Evaluation of farnesol orally and topically against experimental cutaneous leishmaniasis: In -vivo analysis.

Leishmaniasis is a zoonotic disease transmitted by an obligate intra-macrophage protozoan of the genus Leishmania through the infective bite of a vector sandfly. This study investigated the therapeutic efficacy of farnesol, a sesquiterpene compound, for the treatment of cutaneous leishmaniasis (CL) using in vivo BALB/c mouse model. In this study, farnesol's efficacy was compared with the standard drug, paromomycin. It was observed that farnesol significantly reduced lesion sizes and footpad thickness compared to the control group (paromomycin). Lymph node size was also significantly reduced in farnesol-treated mice, indicating its ability to control infection spread. Combination therapy with farnesol and Paromomycin did not demonstrate synergistic effects. These results highlight the potential of farnesol as an alternative therapeutic agent for CL. Further investigations are required to elucidate its mechanism of action and assess potential off-target effects. Optimization of oral delivery methods should be explored to enhance bioavailability. Overall, our findings support farnesol's efficacy in CL treatment, offering promising prospects for improved disease management.

Gallbladder reporting and data system (GB-RADS) for risk stratification of gallbladder wall thickening on ultrasonography: an international expert consensus.

The Gallbladder Reporting and Data System (GB-RADS) ultrasound (US) risk stratification is proposed to improve consistency in US interpretations, reporting, and assessment of risk of malignancy in gallbladder wall thickening in non-acute setting. It was developed based on a systematic review of the literature and the consensus of an international multidisciplinary committee comprising expert radiologists, gastroenterologists, gastrointestinal surgeons, surgical oncologists, medical oncologists, and pathologists using modified Delphi method. For risk stratification, the GB-RADS system recommends six categories (GB-RADS 0-5) of gallbladder wall thickening with gradually increasing risk of malignancy. GB-RADS is based on gallbladder wall features on US including symmetry and extent (focal vs. circumferential) of involvement, layered appearance, intramural features (including intramural cysts and echogenic foci), and interface with the liver. GB-RADS represents the first collaborative effort at risk stratifying the gallbladder wall thickening. This concept is in line with the other US-based risk stratification systems which have been shown to increase the accuracy of detection of malignant lesions and improve management.

Fine needle aspiration cytology with the aid of immunocytochemistry on cell-block confirms the diagnosis of solid pseudopapillary neoplasm of the pancreas.

INTRODUCTION: To determine the diagnostic efficacy of fine needle aspiration cytology (FNAC) in cases of pancreatic solid pseudopapillary neoplasm (PSPN) with emphasis on the cytomorphological features and to evaluate the contribution of immunocytochemistry on FNAC cell-block (CB) in cases of PSPN. METHODS: It is a retrospective study in which ultrasound-guided FNAC of pancreatic lesions diagnosed as PSPN between years 2009 and July 2019 were reviewed along with cytohistological correlation. Immunocytochemistry on CB was performed, wherever required. RESULTS: A total of 16 patients with a cytological diagnosis of PSPN of the pancreas were identified. The most common cytological findings were characteristic branching pseudopapillary fragments with central thin, delicate capillaries associated with the amorphous myxoid substance, surrounded by tumour cells with mild pleomorphism. Immunocytochemistry was performed on CB of six cases. The tumour cells revealed nucleocytoplasmic positivity for ß-catenin, cytoplasmic positivity for vimentin, membranocytoplasmic positivity for CD10 and nuclear positivity for progesterone receptor in all the cases, while they were negative for chromogranin, CD56, pan-cytokeratin and epithelial membrane antigen. The resected histopathological specimen was available in 10cases, and all were confirmed as PSPN. CONCLUSION: Although PSPN has a characteristic cytomorphology, cell-block immunocytochemistry on FNA material confirms the diagnosis in problematic cases and excludes other pancreatic tumours, thus helping in appropriate management.

Pediatric inflammatory myofibroblastic tumor of the trachea: Imaging spectrum and review of literature.

Inflammatory myofibroblastic tumor of the airway is a very uncommon benign primary neoplasm in pediatric age group with increased local recurrence rate and potential metastatic spread. We describe a case of a 6-year boy who was brought to the pediatric emergency with severe respiratory distress, dry cough, and stridor. Contrast-enhanced computed tomography and magnetic resonance imaging (MRI) of the neck showed a polypoidal mass lesion in the right anterolateral trachea causing significant airway narrowing. Bronchoscopic findings correlated with the imaging. The lesion was confirmed at surgery and was completely removed by surgical excision. Histopathology revealed an inflammatory myofibroblastic tumor. MRI findings of this entity in a child have not been reported before.

Aggressive angiomyxoma of transplanted kidney mimicking posttransplant lymphoproliferative disorder.

Angiomyxoma is a scarce neoplasm arising from the soft tissues of perineum and pelvis, more commonly seen in the females. For such a tumor to arise in a renal allograft is rare and has previously been reported only in few case. We report a case of aggressive angiomyxoma arising de novo in the renal allograft nine-year posttransplantation. We describe its imaging features on ultrasound and computed tomography which closely mimic the more usual tumor of the transplanted kidney, posttransplant lymphoproliferative disorder and suggest that angiomyxoma may be considered as a differential diagnosis in a case of soft tissue mass arising within the renal allograft.

Osteoblastic meningioma with turtle shell: Different entity from calcified meningioma.

Bone formation within meningioma is secondary to metaplasia of the meningothelial cells into osteoblastic cells. This needs to be differentiated form the commonly seen calcification. We describe a rare case of osteobalstic meningioma in which bony trabeculae were seen within meningothelial cells.

Mucinous adenocarcinoma of the rectum: a poor candidate for neo-adjuvant chemoradiation?

BACKGROUND: Mucinous adenocarcinoma (MA) is a distinct pathological entity associated with poor outcome. Due to different biological behavior, the response to neoadjuvant chemo-radiation (NACRT) may be inferior compared to non-mucinous tumours. In this study we compare the pathological response of mucinous tumours after NACRT. METHODS: A total of 183 patients who underwent NACRT for rectal cancer were classified as mucinous and non-MAs. The dose of radiation was 45 Gy (at 1.8 Gy per fraction) delivered over five weeks with weekly 5-flourouracil (5-FU) (325 mg/m(2)) and leucovorin (20 mg/m(2)). After surgery, the pathological specimens were evaluated and staged. The data are reported as descriptive statistics and chi-square test used to determine difference in proportions. RESULTS: The two varieties were comparable on the basis of the computed tomography (CT) scan in terms of tumour size and lymph node metastasis. However in terms of pathological response, it was seen that there was a higher incidence of pT4 tumours (73.5% vs. 10.7%), margin positivity (11.7% vs. 2.3%) and advanced nodal disease pN2 (29.4% vs. 9.3%) in mucinous and non-mucinous tumours respectively. CONCLUSIONS: MA of the rectum show a poor response to NACRT as seen in terms of larger residual tumours, higher incidence of margin positivity, and greater residual nodal disease. Also they showed higher incidence of peritoneal and distant dissemination during NACRT. The role of NACRT in mucinous carcinoma of the rectum is of questionable benefit and needs to be examined in prospective trials.

Olfactory region schwannoma: Excision with preservation of olfaction.

Olfactory region schwannomas are rare, but when they occur, they commonly arise from the meningeal branches of the trigeminal nerve and may present without involvement of the olfaction. A 24 year old lady presented with hemifacial paraesthesias. Radiology revealed a large olfactory region enhancing lesion. She was operated through a transbasal with olfactory preserving approach. This manuscript highlights the importance of olfactory preservation in such lesions.

Aceclofenac-induced acute tubulointerstitial nephritis in a patient with diabetes.

We describe a case of a 40-year-old lady diabetic and hypertensive, who presented with increasing fatigue and decreased physical endurance attributable to deterioration in renal function. The renal biopsy revealed drug-induced acute tubulointerstitial nephritis and the chronology of the events suggested the aetiology to be a recent intake of aceclofenac for knee pain. The patient improved with oral corticosteroids and the renal functions returned to baseline in 3 weeks. We did not come across a case of aceclofenac-induced acute tubulointerstitial nephritis on extensive electronic search of literature. This is probably the first case report of acute tubulointerstitial nephritis associated with the use of aceclofenac, a newer potent non-steroidal anti-inflammatory drug.

Mechanistic insights of intestinal absorption and renal conservation of folate in chronic alcoholism.

Folate mediated one-carbon metabolism is of fundamental importance for various cellular processes, including DNA synthesis and methylation of biological molecules. Due to the exogenous requirement of folate in mammals, there exists a well developed epithelial folate transport system for regulation of normal folate homeostasis. The intestinal and renal folate uptake is tightly and diversely regulated and disturbances in folate homeostasis like in alcoholism have pathological consequences. The study was sought to delineate the regulatory mechanism of folate uptake in intestine and reabsorption in renal tubular cells that could evaluate insights of malabsorption during alcoholism. The folate transporters PCFT and RFC were found to be associated with lipid rafts of membrane surfaces in intestine and kidney. Importantly, the observed lower intestinal and renal folate uptake was associated with decreased levels of folate transporter viz. PCFT and RFC in lipid rafts of intestinal and renal membrane surfaces. The decreased association of folate transporters in lipid rafts was associated with decreased protein and mRNA levels. In addition, immunohistochemical studies showed that alcoholic conditions deranged that localization of PCFT and RFC. These findings could explain the possible mechanistic insights that may result in folate malabsorption during alcoholism.

Decreased activity of folate transporters in lipid rafts resulted in reduced hepatic folate uptake in chronic alcoholism in rats.

Folic acid is an essential nutrient that is required for one-carbon biosynthetic processes and for methylation of biomolecules. Deficiency of this micronutrient leads to disturbances in normal physiology of cell. Chronic alcoholism is well known to be associated with folate deficiency, which is due in part to folate malabsorption. The present study deals with the regulatory mechanisms of folate uptake in liver during chronic alcoholism. Male Wistar rats were fed 1 g/kg body weight/day ethanol (20 % solution) orally for 3 months, and the molecular mechanisms of folate uptake were studied in liver. The characterization of the folate transport system in liver basolateral membrane (BLM) suggested it to be a carrier mediated and acidic pH dependent, with the major involvement of proton coupled folate transporter and folate binding protein in the uptake. The folate transporters were found to be associated with lipid raft microdomain of liver BLM. Moreover, ethanol ingestion decreased the folate transport by altering the Vmax of folate transport process and downregulated the expression of folate transporters in lipid rafts. The decreased transporter levels were associated with reduced protein and mRNA levels of these transporters in liver. The deranged folate uptake together with reduced folate transporter levels in lipid rafts resulted in reduced folate levels in liver and thereby to its reduced levels in serum of ethanol-fed rats. The chronic ethanol ingestion led to decreased folate uptake in liver, which was associated with the decreased number of transporter molecules in the lipid rafts that can be ascribed to the reduced synthesis of these transporters.

Biochemical and molecular mechanisms of folate transport in rat pancreas; interference with ethanol ingestion.

Folic acid is an essential nutrient that is required for one-carbon biosynthetic processes and for methylation of biomolecules. Deficiency of this micronutrient leads to disturbances in normal physiology of cell. Chronic alcoholism is well known to be associated with folate deficiency which is due, in part to folate malabsorption. The present study deals with the mechanistic insights of reduced folate absorption in pancreas during chronic alcoholism. Male Wistar rats were fed 1 g/kg body weight/day ethanol (20% solution) orally for 3 months and the mechanisms of alcohol associated reduced folate uptake was studied in pancreas. The folate transport system in the pancreatic plasma membrane (PPM) was found to be acidic pH dependent one. The transporters proton coupled folate transporter (PCFT) and reduced folate carrier (RFC) are involved in folate uptake across PPM. The folate transporters were found to be associated with lipid raft microdomain of the PPM. Ethanol ingestion decreased the folate transport by reducing the levels of folate transporter molecules in lipid rafts at the PPM. The decreased transport efficiency of the PPM was reflected as reduced folate levels in pancreas. The chronic ethanol ingestion led to decreased pancreatic folate uptake. The decreased levels of PCFT and RFC expression in rat PPM were due to decreased association of these proteins with lipid rafts (LR) at the PPM.

Functional and morphological alterations in small intestine mucosa of chronic alcoholics.

BACKGROUND AND AIM: Alcohol-related diseases constitute the third largest health problem after heart disease and cancer in the world. The objective was to study the effects of chronic alcohol intake on small bowel cellular functions with focus on brush border enzymes, membrane enzymes, cellular enzymes and their relationship with structural changes in small bowel mucosa of chronic alcoholics. METHODS: Duodenal biopsies were obtained by upper gastrointestinal endoscopy of chronic alcoholics having alcoholic liver disease (ALD) with and without cirrhosis. The biopsies were then processed for enzymatic assays to analyze the status of cellular functions. Light microscopy, transmission electron microscopy, and scanning electron microscopy were done to study the morphological alterations. Control group consisted of nonalcoholic gastroesophageal reflux disease patients reporting for routine endoscopy. RESULTS: The experimental group consisted of ALD patients which showed significant difference (P < 0.01) in cellular functions when compared with controls. The light microscopy showed partial villous atrophy, increase in lamina propria infiltrate, and intraepithelial lymphocytes as main findings in the alcoholic group. Ultrastructural evaluation revealed changes like widened intercellular junction, distorted microvilli, increased rough endoplasmic reticulum, and increased and dilated mitochondria. The enzyme parameters correlated positively with the mucosal morphology parameters indicating a direct relationship. CONCLUSION: The study brought out the changes in small bowel of chronic alcoholics having ALD at both cellular and subcellular levels which correlated significantly.

FNAC in a case of NHL presenting initially as nodal infarction.

Lymph node infarction is rare and can occur in either nonneoplastic or neoplastic conditions. Fine needle aspiration cytology (FNAC) of infarction preceding lymphoma has not been described earlier. A 26-year-old male, was referred to the cytology laboratory for FNAC of bilateral axillary lymph nodes. FNA smears showed uniform looking ghost cells. There were no viable cells. A biopsy was advised which also showed extensive coagulative necrosis. Five weeks later, right cervical lymph nodes also appeared and FNA smears showed discrete monomorphic population of immature lymphoid cells. A cytologic diagnosis of infarction in a case of non-Hodgkin's lymphoma (NHL) was made and subsequently confirmed by histopathologic examination. Our case indicates that such cases should be followed up closely and repeated aspirations should be done to prevent a delayed diagnosis of lymphoma.

Fibrosing cholestatic hepatitis-like syndrome in a hepatitis B virus and hepatitis C virus-negative renal transplant recipient: a case report with autopsy findings.

We report a patient with fibrosing cholestatic hepatitis (FCH)-like syndrome in renal transplant recipient, who was negative for hepatitis-B and C-virus infection. The patient presented initially with extrahepatic biliary obstruction due to stricture at the lower end of the common bile duct. Cholestasis persisted inspite of effective biliary drainage. He was operated for empyema of the gallbladder and histological examination showed the presence of cytomegalovirus inclusions in the wall of the gallbladder. The patient died inspite of aggressive management; autopsy examination of the liver revealed evidence of FCH-like changes.