This comprehensive review explores the intricate relationship between nutrition,the gut microbiome,steroid hormones,and Parkinson's disease within the context of the gut-brain axis.The gut-brain axis plays a pivot...This comprehensive review explores the intricate relationship between nutrition,the gut microbiome,steroid hormones,and Parkinson's disease within the context of the gut-brain axis.The gut-brain axis plays a pivotal role in neurodegenerative diseases like Parkinson's disease,encompassing diverse components such as the gut microbiota,immune system,metabolism,and neural pathways.The gut microbiome,profoundly influenced by dietary factors,emerges as a key player.Nutrition during the first 1000 days of life shapes the gut microbiota composition,influencing immune responses and impacting both child development and adult health.High-fat,high-sugar diets can disrupt this delicate balance,contributing to inflammation and immune dysfunction.Exploring nutritional strategies,the Mediterranean diet's anti-inflammatory and antioxidant properties show promise in reducing Parkinson's disease risk.Microbiome-targeted dietary approaches and the ketogenic diet hold the potential in improving brain disorders.Beyond nutrition,emerging research uncovers potential interactions between steroid hormones,nutrition,and Parkinson's disease.Progesterone,with its anti-inflammatory properties and presence in the nervous system,offers a novel option for Parkinson's disease therapy.Its ability to enhance neuroprotection within the enteric nervous system presents exciting prospects.The review addresses the hypothesis thatα-synuclein aggregates originate from the gut and may enter the brain via the vagus nerve.Gastrointestinal symptoms preceding motor symptoms support this hypothesis.Dysfunctional gut-brain signaling during gut dysbiosis contributes to inflammation and neurotransmitter imbalances,emphasizing the potential of microbiota-based interventions.In summary,this review uncovers the complex web of interactions between nutrition,the gut microbiome,steroid hormones,and Parkinson's disease within the gut-brain axis framework.Understanding these connections not only offers novel therapeutic insights but also illuminates the origins of neurodegenerative diseases such as Parkinson's disease.展开更多
We describe the clinical, imaging and cytopathological features of solid pseudopapillary tumor of the pancreas (SPTP) diagnosed by endoscopic ultrasound- guided (EUS-guided) fine-needle aspiration (FNA). A 17-year-old...We describe the clinical, imaging and cytopathological features of solid pseudopapillary tumor of the pancreas (SPTP) diagnosed by endoscopic ultrasound- guided (EUS-guided) fine-needle aspiration (FNA). A 17-year-old woman was admitted to our hospital with complaints of an unexplained episodic abdominal pain for 2 mo and a short history of hypertension in the endocrinology clinic. Clinical laboratory examinations revealed polycystic ovary syndrome, splenomegaly and low serum amylase and carcinoembryonic antigen (CEA) levels. Computed tomography (CT) analysis revealed a mass of the pancreatic tail with solid and cystic consistency. EUS confirmed the mass, both in body and tail of the pancreas, with distinct borders, which caused dilation of the peripheral part of the pancreatic duct (major diameter 3.7 mm). The patient underwent EUS-FNA. EUS-FNA cytology specimens consisted of single cells and aggregates of uniform malignant cells, forming microadenoid structures, branching, papillary clusters with delicate fibrovascular cores and nuclear overlapping. Naked capillaries were also seen. The nuclei of malignant cells were round or oval, eccentric with fine granular chromatin, small nucleoli and nuclear grooves in some of them. The malignant cells were periodic acid Schiff (PAS)-Alcian blue (+) and immunocytochemically they were vimentin (+), CA 19.9 (+), synaptophysin (+), chromogranin (-), neuro-specific enolase (-), a1- antitrypsin and a1-antichymotrypsin focal positive. Cytologic findings were strongly suggestive of SPTP. Biopsy confirmed the above cytologic diagnosis. EUS- guided FNA diagnosis of SPTP is accurate. EUS findings,cytomorphologic features and immunostains of cell block help distinguish SPTP from pancreatic endocrine tumors, acinar cell carcinoma and papillary mucinous carcinoma.展开更多
Great advances in screening have lowered the death rate from cervical cancer in the advanced countries. The major advances in cervical cancer screening include the Papanicolaou (Pap) test and liquid-based cytology (LB...Great advances in screening have lowered the death rate from cervical cancer in the advanced countries. The major advances in cervical cancer screening include the Papanicolaou (Pap) test and liquid-based cytology (LBC). In this study, we aimed to use cell remnants from LBC specimens from uterine cervix and endometrium, aspirates from breast and thyroid tumors, and liquid samples (ascites, pleural effusion, and urine). Cell blocks made from cell remnants of LBC specimens were immunohistochemically or immunocytochemically stained for several biomarkers including certain tumor markers such together with hematoxylin and eosin staining for accurate diagnosis of malignancies in different samples. The findings from the cell blocks stained with these biomarkers combined with those from Pap stain led to easily diagnosis of the presence or absence of malignancies. Our findings suggest the utility of LBC and cell blocks from cell remnants in cytologic diagnosis in certain specimens.展开更多
Impaired axonal transport has been observed in patients with amyotrophic lateral sclerosis(ALS)and in animal models,suggesting that transport proteins likely play a critical role in the pathological mechanism of ALS.D...Impaired axonal transport has been observed in patients with amyotrophic lateral sclerosis(ALS)and in animal models,suggesting that transport proteins likely play a critical role in the pathological mechanism of ALS.Dysregulation of Kinesin-family-member 5α(Kif5α),a neuron-specific isoform of heavy chain kinesin family,has been described in several neurological disorders,in humans and animal models,including ALS.In this study,we determined Kif5αexpression by gene sequencing,quantitative reverse transcription-polymerase chain reaction,and western blot assay in the cervical spinal cord of wobbler mice and immunofluorescence staining in dissociated cultures of the ventral horn.Further,we observed the distribution of Kif5αand mitochondria along motor neuronal branches by confocal imaging.Our results showed that Kif5αexpression was greatly dysregulated in wobbler mice,which resulted in altered distribution of Kif5αalong motor neuronal branches with an abnormal mitochondrial distribution.Thus,our results indicate that dysregulation of Kif5 and therefore abnormal transport in motor neuronal branches in this ALS model could be causative for several pathological findings at the cellular level,like misallocation of cytoskeletal proteins or organelles like mitochondria.展开更多
Oxygen is essential to the human life and life of all aerobic organisms. The complete oxidation of nutrients for the biological energy supply is one of the most important prerequisites for the formation of higher life...Oxygen is essential to the human life and life of all aerobic organisms. The complete oxidation of nutrients for the biological energy supply is one of the most important prerequisites for the formation of higher life forms. However, cells that benefit from oxidative respiration also suffer from reactive oxygen species because they adapted to oxygen as an energy source. Healthy cells balance the formation and elimination of reactive oxygen species thereby creating and keeping reactive oxygen species-homeostasis. When the concentration of free radicals exceeds a critical level and homeostasis is disturbed, oxidative stress occurs leading to damage of multiple cellular molecules and compartments. Therefore, oxidative stress plays an important role in the physiology and pathology of various diseases. Often, the antioxidant protection system becomes pathologically unbalanced in the genesis of several diseases, leading to functional losses of the organism, as in the case of amyotrophic lateral sclerosis, or cells develop metabolic mechanisms to use this system as protection against external influences, such as in the case of glioblastoma cells. Either way, understanding the underlying deregulated mechanisms of the oxidative protection system would allow the development of novel treatment strategies for various diseases. Thus, regardless of the direction in which the reactive oxygen species-homeostasis disequilibrate, the focus should be on the oxidative protection system.展开更多
AIM: To study the long-term effects of endoscopic sphincterotomy on biliary epithelium. METHODS: This is a prospective case-control study. A total of 25 patients with a median age of 71 years (range 49-89 years) and p...AIM: To study the long-term effects of endoscopic sphincterotomy on biliary epithelium. METHODS: This is a prospective case-control study. A total of 25 patients with a median age of 71 years (range 49-89 years) and prior endoscopic sphincterotomy (ES) for benign disease formed the fi rst group. The median time from ES was 42 mo (range 8-144 mo). Another 25 patients with a median age of 76 years (range 44-94 mo) and similar characteristics who underwent current endoscopic retrograde cholangio-pancreatography (ERCP) and ES for benign disease formed the second group (control group). Brush cytology of the biliary tree with p53 immunocytology was performed in all patients of both groups. ERCPs and recruitment were conducted at the Endoscopic Unit of Aretaieion University Hospital and Tzaneio Hospital, Athens, from October 2006 to June 2010. RESULTS: No cases were positive or suspicious for malignancy. Epithelial atypia was higher in the first group (32% vs 8% in the second group, P = 0.034). Acute cholangitis and previous biliary operation rates were also higher in the fi rst group (acute cholangitis, 60% vs 24% in the second group, P = 0.01; previous biliary operation, 76% vs 24% in the second group, P = 0.001). Subgroup analysis showed that previous ES was the main causal factor for atypia, which was not related to the time interval from the ES (P = 0.407). Two patients (8%) with atypia in the fi rst group were p53-positive. CONCLUSION: ES causes biliary epithelial atypia that represents mostly reactive/proliferative rather than premalignant changes. The role of p53 immunoreactivity in biliary atypia needs to be further studied.展开更多
Plasticity of cerebellar Purkinje cells(PC)is influenced by progeste rone via the classical progeste rone receptors PR-A and PR-B by stimulating dendritogenesis,spinogenesis,and synaptogenesis in these cells.Dissociat...Plasticity of cerebellar Purkinje cells(PC)is influenced by progeste rone via the classical progeste rone receptors PR-A and PR-B by stimulating dendritogenesis,spinogenesis,and synaptogenesis in these cells.Dissociated PC cultures were used to analyze progeste rone effects at a molecular level on the voltage-gated T-type-Ca^(2+)-channels Ca_(v)3.1,Ca_(v)3.2,and Ca_(v)3.3 as they helped determine neuronal plasticity by regulating Ca^(2+)-influx in neuronal cells.The results showed direct effects of progesterone on the mRNA expression of T-type-Ca^(2+)-channels,as well as on the protein kinases A and C being involved in downstream signaling pathways that play an important role in neuronal plasticity.For the mRNA expression studies of T-type-Ca^(2+)-channels and protein kinases of the signaling cascade,laser microdissection and purified PC cultures of diffe rent maturation stages were used.Immunohistochemical staining was also performed to characte rize the localization of T-type-Ca^(2+)-channels in PC.Expe rimental progesterone treatment was performed on the purified PC culture for 24 and 48 hours.Our results show that progesterone increases the expression of Ca_(v)3.1 and Ca_(v)3.3 and associated protein kinases A and Cin PC at the mRNA level within 48 hours after treatment at latest.These effects extend the current knowledge of the function of progesterone in the central nervous system and provide an explanatory approach for its influence on neuronal plasticity.展开更多
AIM: To study clinical outcomes and management of lymph nodes extrapulmonary small cell carcinoma(LNEPSCC). METHODS: Herein, we perform a systematic search of published literature in the PubMed and EMBASE databases fo...AIM: To study clinical outcomes and management of lymph nodes extrapulmonary small cell carcinoma(LNEPSCC). METHODS: Herein, we perform a systematic search of published literature in the PubMed and EMBASE databases for studies describing LNEPSCC. For uniformity of reporting, LNEPSCC was staged as limited if it involved either single lymph node station or if surgery with curative intent had been undertaken. The disease was staged extensive if it involved two or more lymph node regions.RESULTS: The systematic literature review yielded eight descriptions(n = 14) involving cervical, submandibular and inguinal lymph nodes. Eleven(64.7%) patients had limited disease(LD) and six(35.3%) had extensive disease(ED) at presentation. Chemotherapy(n = 6, 35.3%) or surgery(n = 4, 23.5%) were the most common form of treatment given to these patients. Complete response was achieved in 12(70.6%) of the patients. Median(interquartile range) progression free survival and overall survival was 15(7-42) mo and 22(12.75-42) mo respectively. Of the three illustrative cases, two patients each had ED at presentation and achieved complete remission with platinum based combination chemotherapy.CONCLUSION: LNEPSCC is a rare disease with less than 15 reported cases in world literature. Surgical resection with curative intent is feasible in those with LD while platinum based combination chemoradiation is associated with favorable outcomes in patients with ED. Prognosis of LNEPSCC is better than that of small cell lung cancer in general.展开更多
Glioblastoma multiforme(GBM) is a highly aggressive glial brain tumor with an unfavorable prognosis despite all current therapies including surgery, radiation and chemotherapy. One characteristic of this tumor is a st...Glioblastoma multiforme(GBM) is a highly aggressive glial brain tumor with an unfavorable prognosis despite all current therapies including surgery, radiation and chemotherapy. One characteristic of this tumor is a strong synthesis of vascular endothelial growth factor(VEGF), an angiogenesis factor, followed by pronounced vascularization. VEGF became a target in the treatment of GBM, for example with bevacizumab or the tyrosine kinase inhibitor axitinib, which blocks VEGF receptors. To improve patients' prognosis, new targets in the treatment of GBM are under investigations. The role of gap junctions in GBM remains unknown, but some experimental therapies affect these intercellular channels to treat the tumor. Gap junctions are composed of connexins to allow the transport of small molecules between adjacent cells through gap junctional intercellular communication(GJIC). Based on data derived from astrocytes in former studies, which show that VEGF is able to enhance GJIC, the current study analyzed the effects of VEGF, radiation therapy and VEGF receptor blockade by axitinib on GJIC in human GBM cell lines U-87 and U-251. While VEGF is able to induce GJIC in U-251 cells but not in U-87 cells, radiation enhances GJIC in both cell lines. VEGF receptor blockade by axitinib diminishes radiation induced effects in U-251 partially, while increases GJIC in U-87 cells. Our data indicate that VEGF and radiation are both modifying components of GJIC in pathologic brain tumor tissue.展开更多
Leptomeningeal carcinomatosis is a very rare manifestation in patients diagnosed with esophagogastric junction and gastric cancer. Its prognosis is ominous and therapy outcomes are disappointing. Herein, we present tw...Leptomeningeal carcinomatosis is a very rare manifestation in patients diagnosed with esophagogastric junction and gastric cancer. Its prognosis is ominous and therapy outcomes are disappointing. Herein, we present two patients; one initially diagnosed with gastric cancer and leptomeningeal carcinomatosis but no other evidence of metastatic disease and the other one initially diagnosed with esophagogastric junction cancer, who recurred solitary with leptomeningeal seedings several years after the initial diagnosis and treatment. Furthermore, a thorough and short review of the literature is carried out.展开更多
The nervous system is a highly complex organization composed of its basicunit,the neuronal cells,and specialized supporting cells,the glial cells.The main glial cells in the central nervous system(CNS)are astrocytes,m...The nervous system is a highly complex organization composed of its basicunit,the neuronal cells,and specialized supporting cells,the glial cells.The main glial cells in the central nervous system(CNS)are astrocytes,microglia and oligodendrocytes.Astrocytes are the most abundant glial cell type in the CNS.展开更多
AIM:To determine the histopathological changes of rifampicin applied intravitreally on retinal ganglion cells by means of stereological and histopathological methods.METHODS:For this study twenty-four New Zealand adul...AIM:To determine the histopathological changes of rifampicin applied intravitreally on retinal ganglion cells by means of stereological and histopathological methods.METHODS:For this study twenty-four New Zealand adult rabbits were divided into four groups(n=6 for each group).50μg/0.1mL(group 1),100μg/0.1mL(group 2),150μg/0.1mL(group 3) and 200μg/0.1mL(group 4),rifampicin were injected into the vitreous of the right eyes of animals,their left eyes were used as control(group 5).After the 28thday of application,animals were anesthetised with xylazine(8mg/kg,IM) and then their eyes were enucleated immediately.Patterns were taken away and eyes were prepared for both stereological and electromicroscopic observation.RESULTS:Depending on the high dose of rifampicin,some histopathological changes such as cytoplasmic dilatation and damaged membrane were observed on the electromicroscopic level.Using quantitative examination,which was done at the light microscopic level,it was shown that the number of neurons decreased linearly as rifampicin dose increased when compared with the control group.CONCLUSION:Based on these findings,low-dose rifampicin(50μg/0.1mL) may be useful for treatment of the ocular diseases.展开更多
A 71-year-old man, with history of plasmacytoma in relapse since one year, was hospitalized for a initial presentation of acute pancreatitis and hepatitis.Although there was a heterogeneous infiltration around the pan...A 71-year-old man, with history of plasmacytoma in relapse since one year, was hospitalized for a initial presentation of acute pancreatitis and hepatitis.Although there was a heterogeneous infiltration around the pancreas head, the diagnosis of an extramedullary localization of his plasmacytoma was not made until later.This delayed diagnosis was due to the lack of specific radiologic features and the lack of dilatation of biliary ducts at the admission.A diagnosis was made with a simple ultrasound guided paracentesis of the low abundance ascites after a transjugular hepatic biopsy, an endoscopic ultrasound-guided fine needle aspiration of the pancreatic mass, and a failed attempt of biliary drainage through endoscopic retrograde cholangiopancreatography.In order to document the difficulty of this diagnosis, characteristics of 63 patients suffering from this condition and diagnosis were identified and discussed through a systematic literature search.展开更多
AIM:To measure the dose distribution,related to the treatment planning calculations,in the contralateral mammary gland of breast cancer patients treated with accelerated hypofractionated 3-dimensional conformal radiot...AIM:To measure the dose distribution,related to the treatment planning calculations,in the contralateral mammary gland of breast cancer patients treated with accelerated hypofractionated 3-dimensional conformal radiotherapy.METHODS:Thirty-four prospectively selected female patients with right breast cancer (pN0,negative surgical margins) were treated with breast-conserving surgery.A total dose of 42.5 Gy (2.66 Gy/fraction) was prescribed;it was requested that planning target volumes be covered by the 95% isodose line.The contralateral mam-mary gland was defined on CT simulation.The dose received was evaluated by dose volume histograms.RESULTS:The measured contralateral breast doses were:(1) Dose maximum:290-448 cGy [Equivalent (Eq) 337-522 cGy];(2) Mean dose:45-70 cGy (Eq 524815 cGy);and (3) Median dose:29-47 cGy (337-547 cGy) for total primary breast dose of 42.5 Gy in 16 equal fractions.The spearman rho correlation showed statistical significance between the contralateral breast volume and maximum dose (P=0.0292),as well as mean dose (P=0.0025) and median dose (P=0.046) to the breast.CONCLUSION:Minimizing the dose to the contralateral breast has to be one of the priorities of the radiation oncologist when using short schedules because of the radiosensitivity of this organ at risk.Further study is necessary to assess the long-term clinical impact of this schedule.展开更多
Objective:To evaluate the changes occur in the vagina, cervix and endometrium during the pre- ovulatory period in Arabian mares by using endoscope as a diagnostic tool as well as the availability of taking an endoscop...Objective:To evaluate the changes occur in the vagina, cervix and endometrium during the pre- ovulatory period in Arabian mares by using endoscope as a diagnostic tool as well as the availability of taking an endoscopic biopsy during this stage.Methods:Ten cyclic and healthy arabian mares were subjected to ultrasound scanning of their ovaries to estimate the diameter of the preovulatory follicles, collection of blood samples for estimating the hormonal levels (Estradiol-17β and progestrone) for confirming the estrous phase, endoscopic monitoring their vagina, cervix and endometrium, the availability of taking biopsical samples and histological examination of the obtained samples.Results:The obtained data revealed that, the mean diameter of the preovulatory follicles was (3.95±0.34) cm, the plasma estradiol and progestrone levels were (85.98±5.26) pg/mL and (0.73±0.23) ng/mL, respectively, endoscopic monitoring the vagina, cervix and endometrium revealed hyperemic vaginal mucous membrane, soft and opened cervical ostium with abundant estrous mucous and folding, hyperemic and edematous appearance of the endometrium, respectively and the histological features of the biopsical endometrial samples revealed that, The lamina propria-sub mucosa was packed with simple or branched tubular glands lined with simple columnar epithelium showing oval or rounded dark nuclei with different degrees of secretory activities of the glands.Conclusions: The endoscope proved to be a reliable tool for confirming the estrous phase in mares and monitoring the gross features of the vagina, the cervix and the endometrium, in addition to the availability of taking biopsical smears.展开更多
Neurolymphomatosis, defined as invasion of cranial nerves and peripheral nerve roots, plexus or nerves by Non Hodgkin’s Lymphoma is a very rare clinical entity. We describe a case of 69 years old gentleman, who prese...Neurolymphomatosis, defined as invasion of cranial nerves and peripheral nerve roots, plexus or nerves by Non Hodgkin’s Lymphoma is a very rare clinical entity. We describe a case of 69 years old gentleman, who presented to us with asymmetric, painful sensorimotor polyneuropathy. He was admitted with 2 months history of dry cough, constitutional symptoms, paraesthesias on right side of face along with painful asymmetrical quadriparesis. Nerve conduction studies were suggestive of asymmetrical sensorimotor axonal and demyelinating neuropathy. Cerebrospinal fluid analysis revealed mild pleocytosis with raised protein. FDG-PET showed intense uptake in both adrenals, abdominal lymph nodes, sacral nerve roots and brachial plexus. Fine needle aspiration cytology of adrenal mass revealed evidence of diffuse large B cell Non Hodgkin’s Lymphoma. As patient succumbed to illness, an autopsy was done, which revealed diffuse large B cell lymphoma involving adrenals, brachial and lumbosacral plexuses. Our report provides important insights into a rare cause of painful demyelinating multiple mononeuropathy and emphasises on increasing role and diagnostic utility of PET imaging in evaluation of patients presenting with multiple mononeuropathy, especially with regards to paraneoplastic or neoplastic causes such as lymphoma.展开更多
The CD4+/CD56+ hematodermic neoplasm is a rare aggressive systemic neoplasm for which effective therapies have not yet been established, it is clinically characterized by cutaneous involvement with spread to bone marr...The CD4+/CD56+ hematodermic neoplasm is a rare aggressive systemic neoplasm for which effective therapies have not yet been established, it is clinically characterized by cutaneous involvement with spread to bone marrow, blood and poor prognosis with current chemotherapy regimens. Our objective is to report diagnosis and treatment difficulties of CD4+/CD56+ hematodermic neoplasm. We describe here a Tunisian man who presented with subcutaneous ulcerated lesion localized in the right leg and multiples generalized nodules. Skin biopsy showed an atypical lymphoid cell infiltration with an angiocentric pattern and extensive necrosis by immuno-histochemical analysis, these cells were positive for CD4, CD56, granzyme B and negative for CD8, CD123, CD20 and CD30. T-cell rearrangement and Epstein-Barr-virus (EBV) in situ hybridation studies were negative. The patient underwent 5 cycles chemotherapy SMILE regimen monthly sandwiched with radiotherapy on the residual lesions of the right leg with great tolerance but he relapsed within 8months with skin, blood, bone marrow, lung, and cerebrospinal involvement. Based on these findings, the patient was diagnosed with CD4+/CD56+ hematodermic neoplasm (blastic NK-like T-cell lymphoma) treated with one course of hyper-CVAD regimen, he died within 20 days with a septic chok. Despite the use of L-Asparaginase and radiotherapy the prognosis is very poor;we suggest the exploration for highly active drugs, hematopoietic stem cell transplantation (HSCT) is crucial to improve survival.展开更多
Vascular endothelial growth factor(VEGF)in neurodevelopment and regeneration:VEGF is a well-known factor that promotes vascularization and angiogenesis.Besides this it participates in the pathogenesis of several disea...Vascular endothelial growth factor(VEGF)in neurodevelopment and regeneration:VEGF is a well-known factor that promotes vascularization and angiogenesis.Besides this it participates in the pathogenesis of several diseases,such as colorectal carcinoma,lung cancer or diabetic retinopathy.Within the last decade,VEGF has been successfully integrated into the treatment of such diseases,for example as a therapy for colorectal cancer with the展开更多
文摘This comprehensive review explores the intricate relationship between nutrition,the gut microbiome,steroid hormones,and Parkinson's disease within the context of the gut-brain axis.The gut-brain axis plays a pivotal role in neurodegenerative diseases like Parkinson's disease,encompassing diverse components such as the gut microbiota,immune system,metabolism,and neural pathways.The gut microbiome,profoundly influenced by dietary factors,emerges as a key player.Nutrition during the first 1000 days of life shapes the gut microbiota composition,influencing immune responses and impacting both child development and adult health.High-fat,high-sugar diets can disrupt this delicate balance,contributing to inflammation and immune dysfunction.Exploring nutritional strategies,the Mediterranean diet's anti-inflammatory and antioxidant properties show promise in reducing Parkinson's disease risk.Microbiome-targeted dietary approaches and the ketogenic diet hold the potential in improving brain disorders.Beyond nutrition,emerging research uncovers potential interactions between steroid hormones,nutrition,and Parkinson's disease.Progesterone,with its anti-inflammatory properties and presence in the nervous system,offers a novel option for Parkinson's disease therapy.Its ability to enhance neuroprotection within the enteric nervous system presents exciting prospects.The review addresses the hypothesis thatα-synuclein aggregates originate from the gut and may enter the brain via the vagus nerve.Gastrointestinal symptoms preceding motor symptoms support this hypothesis.Dysfunctional gut-brain signaling during gut dysbiosis contributes to inflammation and neurotransmitter imbalances,emphasizing the potential of microbiota-based interventions.In summary,this review uncovers the complex web of interactions between nutrition,the gut microbiome,steroid hormones,and Parkinson's disease within the gut-brain axis framework.Understanding these connections not only offers novel therapeutic insights but also illuminates the origins of neurodegenerative diseases such as Parkinson's disease.
文摘We describe the clinical, imaging and cytopathological features of solid pseudopapillary tumor of the pancreas (SPTP) diagnosed by endoscopic ultrasound- guided (EUS-guided) fine-needle aspiration (FNA). A 17-year-old woman was admitted to our hospital with complaints of an unexplained episodic abdominal pain for 2 mo and a short history of hypertension in the endocrinology clinic. Clinical laboratory examinations revealed polycystic ovary syndrome, splenomegaly and low serum amylase and carcinoembryonic antigen (CEA) levels. Computed tomography (CT) analysis revealed a mass of the pancreatic tail with solid and cystic consistency. EUS confirmed the mass, both in body and tail of the pancreas, with distinct borders, which caused dilation of the peripheral part of the pancreatic duct (major diameter 3.7 mm). The patient underwent EUS-FNA. EUS-FNA cytology specimens consisted of single cells and aggregates of uniform malignant cells, forming microadenoid structures, branching, papillary clusters with delicate fibrovascular cores and nuclear overlapping. Naked capillaries were also seen. The nuclei of malignant cells were round or oval, eccentric with fine granular chromatin, small nucleoli and nuclear grooves in some of them. The malignant cells were periodic acid Schiff (PAS)-Alcian blue (+) and immunocytochemically they were vimentin (+), CA 19.9 (+), synaptophysin (+), chromogranin (-), neuro-specific enolase (-), a1- antitrypsin and a1-antichymotrypsin focal positive. Cytologic findings were strongly suggestive of SPTP. Biopsy confirmed the above cytologic diagnosis. EUS- guided FNA diagnosis of SPTP is accurate. EUS findings,cytomorphologic features and immunostains of cell block help distinguish SPTP from pancreatic endocrine tumors, acinar cell carcinoma and papillary mucinous carcinoma.
文摘Great advances in screening have lowered the death rate from cervical cancer in the advanced countries. The major advances in cervical cancer screening include the Papanicolaou (Pap) test and liquid-based cytology (LBC). In this study, we aimed to use cell remnants from LBC specimens from uterine cervix and endometrium, aspirates from breast and thyroid tumors, and liquid samples (ascites, pleural effusion, and urine). Cell blocks made from cell remnants of LBC specimens were immunohistochemically or immunocytochemically stained for several biomarkers including certain tumor markers such together with hematoxylin and eosin staining for accurate diagnosis of malignancies in different samples. The findings from the cell blocks stained with these biomarkers combined with those from Pap stain led to easily diagnosis of the presence or absence of malignancies. Our findings suggest the utility of LBC and cell blocks from cell remnants in cytologic diagnosis in certain specimens.
基金supported by FoRUM–F976-20 (Ruhr-University Bochum)(to VM and CT)
文摘Impaired axonal transport has been observed in patients with amyotrophic lateral sclerosis(ALS)and in animal models,suggesting that transport proteins likely play a critical role in the pathological mechanism of ALS.Dysregulation of Kinesin-family-member 5α(Kif5α),a neuron-specific isoform of heavy chain kinesin family,has been described in several neurological disorders,in humans and animal models,including ALS.In this study,we determined Kif5αexpression by gene sequencing,quantitative reverse transcription-polymerase chain reaction,and western blot assay in the cervical spinal cord of wobbler mice and immunofluorescence staining in dissociated cultures of the ventral horn.Further,we observed the distribution of Kif5αand mitochondria along motor neuronal branches by confocal imaging.Our results showed that Kif5αexpression was greatly dysregulated in wobbler mice,which resulted in altered distribution of Kif5αalong motor neuronal branches with an abnormal mitochondrial distribution.Thus,our results indicate that dysregulation of Kif5 and therefore abnormal transport in motor neuronal branches in this ALS model could be causative for several pathological findings at the cellular level,like misallocation of cytoskeletal proteins or organelles like mitochondria.
文摘Oxygen is essential to the human life and life of all aerobic organisms. The complete oxidation of nutrients for the biological energy supply is one of the most important prerequisites for the formation of higher life forms. However, cells that benefit from oxidative respiration also suffer from reactive oxygen species because they adapted to oxygen as an energy source. Healthy cells balance the formation and elimination of reactive oxygen species thereby creating and keeping reactive oxygen species-homeostasis. When the concentration of free radicals exceeds a critical level and homeostasis is disturbed, oxidative stress occurs leading to damage of multiple cellular molecules and compartments. Therefore, oxidative stress plays an important role in the physiology and pathology of various diseases. Often, the antioxidant protection system becomes pathologically unbalanced in the genesis of several diseases, leading to functional losses of the organism, as in the case of amyotrophic lateral sclerosis, or cells develop metabolic mechanisms to use this system as protection against external influences, such as in the case of glioblastoma cells. Either way, understanding the underlying deregulated mechanisms of the oxidative protection system would allow the development of novel treatment strategies for various diseases. Thus, regardless of the direction in which the reactive oxygen species-homeostasis disequilibrate, the focus should be on the oxidative protection system.
基金Supported by GC Medical Hellas who offered us free cytology brushes
文摘AIM: To study the long-term effects of endoscopic sphincterotomy on biliary epithelium. METHODS: This is a prospective case-control study. A total of 25 patients with a median age of 71 years (range 49-89 years) and prior endoscopic sphincterotomy (ES) for benign disease formed the fi rst group. The median time from ES was 42 mo (range 8-144 mo). Another 25 patients with a median age of 76 years (range 44-94 mo) and similar characteristics who underwent current endoscopic retrograde cholangio-pancreatography (ERCP) and ES for benign disease formed the second group (control group). Brush cytology of the biliary tree with p53 immunocytology was performed in all patients of both groups. ERCPs and recruitment were conducted at the Endoscopic Unit of Aretaieion University Hospital and Tzaneio Hospital, Athens, from October 2006 to June 2010. RESULTS: No cases were positive or suspicious for malignancy. Epithelial atypia was higher in the first group (32% vs 8% in the second group, P = 0.034). Acute cholangitis and previous biliary operation rates were also higher in the fi rst group (acute cholangitis, 60% vs 24% in the second group, P = 0.01; previous biliary operation, 76% vs 24% in the second group, P = 0.001). Subgroup analysis showed that previous ES was the main causal factor for atypia, which was not related to the time interval from the ES (P = 0.407). Two patients (8%) with atypia in the fi rst group were p53-positive. CONCLUSION: ES causes biliary epithelial atypia that represents mostly reactive/proliferative rather than premalignant changes. The role of p53 immunoreactivity in biliary atypia needs to be further studied.
文摘Plasticity of cerebellar Purkinje cells(PC)is influenced by progeste rone via the classical progeste rone receptors PR-A and PR-B by stimulating dendritogenesis,spinogenesis,and synaptogenesis in these cells.Dissociated PC cultures were used to analyze progeste rone effects at a molecular level on the voltage-gated T-type-Ca^(2+)-channels Ca_(v)3.1,Ca_(v)3.2,and Ca_(v)3.3 as they helped determine neuronal plasticity by regulating Ca^(2+)-influx in neuronal cells.The results showed direct effects of progesterone on the mRNA expression of T-type-Ca^(2+)-channels,as well as on the protein kinases A and C being involved in downstream signaling pathways that play an important role in neuronal plasticity.For the mRNA expression studies of T-type-Ca^(2+)-channels and protein kinases of the signaling cascade,laser microdissection and purified PC cultures of diffe rent maturation stages were used.Immunohistochemical staining was also performed to characte rize the localization of T-type-Ca^(2+)-channels in PC.Expe rimental progesterone treatment was performed on the purified PC culture for 24 and 48 hours.Our results show that progesterone increases the expression of Ca_(v)3.1 and Ca_(v)3.3 and associated protein kinases A and Cin PC at the mRNA level within 48 hours after treatment at latest.These effects extend the current knowledge of the function of progesterone in the central nervous system and provide an explanatory approach for its influence on neuronal plasticity.
文摘AIM: To study clinical outcomes and management of lymph nodes extrapulmonary small cell carcinoma(LNEPSCC). METHODS: Herein, we perform a systematic search of published literature in the PubMed and EMBASE databases for studies describing LNEPSCC. For uniformity of reporting, LNEPSCC was staged as limited if it involved either single lymph node station or if surgery with curative intent had been undertaken. The disease was staged extensive if it involved two or more lymph node regions.RESULTS: The systematic literature review yielded eight descriptions(n = 14) involving cervical, submandibular and inguinal lymph nodes. Eleven(64.7%) patients had limited disease(LD) and six(35.3%) had extensive disease(ED) at presentation. Chemotherapy(n = 6, 35.3%) or surgery(n = 4, 23.5%) were the most common form of treatment given to these patients. Complete response was achieved in 12(70.6%) of the patients. Median(interquartile range) progression free survival and overall survival was 15(7-42) mo and 22(12.75-42) mo respectively. Of the three illustrative cases, two patients each had ED at presentation and achieved complete remission with platinum based combination chemotherapy.CONCLUSION: LNEPSCC is a rare disease with less than 15 reported cases in world literature. Surgical resection with curative intent is feasible in those with LD while platinum based combination chemoradiation is associated with favorable outcomes in patients with ED. Prognosis of LNEPSCC is better than that of small cell lung cancer in general.
文摘Glioblastoma multiforme(GBM) is a highly aggressive glial brain tumor with an unfavorable prognosis despite all current therapies including surgery, radiation and chemotherapy. One characteristic of this tumor is a strong synthesis of vascular endothelial growth factor(VEGF), an angiogenesis factor, followed by pronounced vascularization. VEGF became a target in the treatment of GBM, for example with bevacizumab or the tyrosine kinase inhibitor axitinib, which blocks VEGF receptors. To improve patients' prognosis, new targets in the treatment of GBM are under investigations. The role of gap junctions in GBM remains unknown, but some experimental therapies affect these intercellular channels to treat the tumor. Gap junctions are composed of connexins to allow the transport of small molecules between adjacent cells through gap junctional intercellular communication(GJIC). Based on data derived from astrocytes in former studies, which show that VEGF is able to enhance GJIC, the current study analyzed the effects of VEGF, radiation therapy and VEGF receptor blockade by axitinib on GJIC in human GBM cell lines U-87 and U-251. While VEGF is able to induce GJIC in U-251 cells but not in U-87 cells, radiation enhances GJIC in both cell lines. VEGF receptor blockade by axitinib diminishes radiation induced effects in U-251 partially, while increases GJIC in U-87 cells. Our data indicate that VEGF and radiation are both modifying components of GJIC in pathologic brain tumor tissue.
文摘Leptomeningeal carcinomatosis is a very rare manifestation in patients diagnosed with esophagogastric junction and gastric cancer. Its prognosis is ominous and therapy outcomes are disappointing. Herein, we present two patients; one initially diagnosed with gastric cancer and leptomeningeal carcinomatosis but no other evidence of metastatic disease and the other one initially diagnosed with esophagogastric junction cancer, who recurred solitary with leptomeningeal seedings several years after the initial diagnosis and treatment. Furthermore, a thorough and short review of the literature is carried out.
基金supported by German Academic Exchange Service to HC。
文摘The nervous system is a highly complex organization composed of its basicunit,the neuronal cells,and specialized supporting cells,the glial cells.The main glial cells in the central nervous system(CNS)are astrocytes,microglia and oligodendrocytes.Astrocytes are the most abundant glial cell type in the CNS.
文摘AIM:To determine the histopathological changes of rifampicin applied intravitreally on retinal ganglion cells by means of stereological and histopathological methods.METHODS:For this study twenty-four New Zealand adult rabbits were divided into four groups(n=6 for each group).50μg/0.1mL(group 1),100μg/0.1mL(group 2),150μg/0.1mL(group 3) and 200μg/0.1mL(group 4),rifampicin were injected into the vitreous of the right eyes of animals,their left eyes were used as control(group 5).After the 28thday of application,animals were anesthetised with xylazine(8mg/kg,IM) and then their eyes were enucleated immediately.Patterns were taken away and eyes were prepared for both stereological and electromicroscopic observation.RESULTS:Depending on the high dose of rifampicin,some histopathological changes such as cytoplasmic dilatation and damaged membrane were observed on the electromicroscopic level.Using quantitative examination,which was done at the light microscopic level,it was shown that the number of neurons decreased linearly as rifampicin dose increased when compared with the control group.CONCLUSION:Based on these findings,low-dose rifampicin(50μg/0.1mL) may be useful for treatment of the ocular diseases.
文摘A 71-year-old man, with history of plasmacytoma in relapse since one year, was hospitalized for a initial presentation of acute pancreatitis and hepatitis.Although there was a heterogeneous infiltration around the pancreas head, the diagnosis of an extramedullary localization of his plasmacytoma was not made until later.This delayed diagnosis was due to the lack of specific radiologic features and the lack of dilatation of biliary ducts at the admission.A diagnosis was made with a simple ultrasound guided paracentesis of the low abundance ascites after a transjugular hepatic biopsy, an endoscopic ultrasound-guided fine needle aspiration of the pancreatic mass, and a failed attempt of biliary drainage through endoscopic retrograde cholangiopancreatography.In order to document the difficulty of this diagnosis, characteristics of 63 patients suffering from this condition and diagnosis were identified and discussed through a systematic literature search.
文摘AIM:To measure the dose distribution,related to the treatment planning calculations,in the contralateral mammary gland of breast cancer patients treated with accelerated hypofractionated 3-dimensional conformal radiotherapy.METHODS:Thirty-four prospectively selected female patients with right breast cancer (pN0,negative surgical margins) were treated with breast-conserving surgery.A total dose of 42.5 Gy (2.66 Gy/fraction) was prescribed;it was requested that planning target volumes be covered by the 95% isodose line.The contralateral mam-mary gland was defined on CT simulation.The dose received was evaluated by dose volume histograms.RESULTS:The measured contralateral breast doses were:(1) Dose maximum:290-448 cGy [Equivalent (Eq) 337-522 cGy];(2) Mean dose:45-70 cGy (Eq 524815 cGy);and (3) Median dose:29-47 cGy (337-547 cGy) for total primary breast dose of 42.5 Gy in 16 equal fractions.The spearman rho correlation showed statistical significance between the contralateral breast volume and maximum dose (P=0.0292),as well as mean dose (P=0.0025) and median dose (P=0.046) to the breast.CONCLUSION:Minimizing the dose to the contralateral breast has to be one of the priorities of the radiation oncologist when using short schedules because of the radiosensitivity of this organ at risk.Further study is necessary to assess the long-term clinical impact of this schedule.
文摘Objective:To evaluate the changes occur in the vagina, cervix and endometrium during the pre- ovulatory period in Arabian mares by using endoscope as a diagnostic tool as well as the availability of taking an endoscopic biopsy during this stage.Methods:Ten cyclic and healthy arabian mares were subjected to ultrasound scanning of their ovaries to estimate the diameter of the preovulatory follicles, collection of blood samples for estimating the hormonal levels (Estradiol-17β and progestrone) for confirming the estrous phase, endoscopic monitoring their vagina, cervix and endometrium, the availability of taking biopsical samples and histological examination of the obtained samples.Results:The obtained data revealed that, the mean diameter of the preovulatory follicles was (3.95±0.34) cm, the plasma estradiol and progestrone levels were (85.98±5.26) pg/mL and (0.73±0.23) ng/mL, respectively, endoscopic monitoring the vagina, cervix and endometrium revealed hyperemic vaginal mucous membrane, soft and opened cervical ostium with abundant estrous mucous and folding, hyperemic and edematous appearance of the endometrium, respectively and the histological features of the biopsical endometrial samples revealed that, The lamina propria-sub mucosa was packed with simple or branched tubular glands lined with simple columnar epithelium showing oval or rounded dark nuclei with different degrees of secretory activities of the glands.Conclusions: The endoscope proved to be a reliable tool for confirming the estrous phase in mares and monitoring the gross features of the vagina, the cervix and the endometrium, in addition to the availability of taking biopsical smears.
文摘Neurolymphomatosis, defined as invasion of cranial nerves and peripheral nerve roots, plexus or nerves by Non Hodgkin’s Lymphoma is a very rare clinical entity. We describe a case of 69 years old gentleman, who presented to us with asymmetric, painful sensorimotor polyneuropathy. He was admitted with 2 months history of dry cough, constitutional symptoms, paraesthesias on right side of face along with painful asymmetrical quadriparesis. Nerve conduction studies were suggestive of asymmetrical sensorimotor axonal and demyelinating neuropathy. Cerebrospinal fluid analysis revealed mild pleocytosis with raised protein. FDG-PET showed intense uptake in both adrenals, abdominal lymph nodes, sacral nerve roots and brachial plexus. Fine needle aspiration cytology of adrenal mass revealed evidence of diffuse large B cell Non Hodgkin’s Lymphoma. As patient succumbed to illness, an autopsy was done, which revealed diffuse large B cell lymphoma involving adrenals, brachial and lumbosacral plexuses. Our report provides important insights into a rare cause of painful demyelinating multiple mononeuropathy and emphasises on increasing role and diagnostic utility of PET imaging in evaluation of patients presenting with multiple mononeuropathy, especially with regards to paraneoplastic or neoplastic causes such as lymphoma.
文摘The CD4+/CD56+ hematodermic neoplasm is a rare aggressive systemic neoplasm for which effective therapies have not yet been established, it is clinically characterized by cutaneous involvement with spread to bone marrow, blood and poor prognosis with current chemotherapy regimens. Our objective is to report diagnosis and treatment difficulties of CD4+/CD56+ hematodermic neoplasm. We describe here a Tunisian man who presented with subcutaneous ulcerated lesion localized in the right leg and multiples generalized nodules. Skin biopsy showed an atypical lymphoid cell infiltration with an angiocentric pattern and extensive necrosis by immuno-histochemical analysis, these cells were positive for CD4, CD56, granzyme B and negative for CD8, CD123, CD20 and CD30. T-cell rearrangement and Epstein-Barr-virus (EBV) in situ hybridation studies were negative. The patient underwent 5 cycles chemotherapy SMILE regimen monthly sandwiched with radiotherapy on the residual lesions of the right leg with great tolerance but he relapsed within 8months with skin, blood, bone marrow, lung, and cerebrospinal involvement. Based on these findings, the patient was diagnosed with CD4+/CD56+ hematodermic neoplasm (blastic NK-like T-cell lymphoma) treated with one course of hyper-CVAD regimen, he died within 20 days with a septic chok. Despite the use of L-Asparaginase and radiotherapy the prognosis is very poor;we suggest the exploration for highly active drugs, hematopoietic stem cell transplantation (HSCT) is crucial to improve survival.
基金the Heinrich and Alma Vogelsang Foundation for financial support in the form of a graduation scholarship
文摘Vascular endothelial growth factor(VEGF)in neurodevelopment and regeneration:VEGF is a well-known factor that promotes vascularization and angiogenesis.Besides this it participates in the pathogenesis of several diseases,such as colorectal carcinoma,lung cancer or diabetic retinopathy.Within the last decade,VEGF has been successfully integrated into the treatment of such diseases,for example as a therapy for colorectal cancer with the
