Status de expressão do receptor de leptina e adiponectina no carcinoma colorretal: A cross-estudo prospectivo seccional / Correlation of leptin and adiponectin receptor expression with clinicopathological parameters in colorectal carcinoma - a cross-sectional prospective study

ABSTRACT Background: Colorectal carcinoma (CRC) is one of the common carcinomas with a rising incidence of metastasis due to its advanced stage of presentation. The existing biomarkers such as CEA (Carcinoembryonic antigen) etc., for prognosis, have low sensitivity and specificity. Hence a need for a newer definitive biomarker. Obesity is the leading cause of CRC. Leptin and adiponectin secreted by adipose tissue have been studied as potential biomarkers in the field of CRC. The present study helps to understand the association of leptin and adiponectin receptors with clinicopathological parameters. Objective: To correlate the various clinicopathological parameters with the tissue expression of leptin and adiponectin receptors in CRC. Methods: It is a cross-sectional prospective study conducted at a tertiary care hospital. Formalin fixed paraffin blocks of all radical resection CRC cases were collected and immunohistochemistry (IHC)was carried out on tumor tissue for leptin and adiponectin receptor. Tumor characteristics and clinical parameters were collected from the hospital medical records. Pearson's correlation coefficient test was used. Results: Immunohistochemistry was performed on 60 cases of CRC. Significant positive correlation of leptin was observed with size, lymph node metastasis, advanced stage, and grade of tumor (P<0.05). A significant correlation between adiponectin receptor and CRC was observed concerning age, stage, lymph node metastasis, distant metastasis and grade of tumor. Conclusion: Positive expression of leptin and negative expression of adiponectin receptors in CRC helps to predict the risk of metastasis.

RESUMO Contexto: O carcinoma colorretal (CCR) é um dos carcinomas comuns com incidência crescente de metástases devido ao seu estágio avançado de apresentação. Os biomarcadores existentes como CEA (antígeno carcinoembrionário) etc., para prognóstico, apresentam baixa sensibilidade e especificidade. Daí a necessidade de um biomarcador definitivo mais recente. A obesidade é a principal causa do CCR. A leptina e a adiponectina secretadas pelo tecido adiposo têm sido estudadas como potenciais biomarcadores na área do CCR. O presente estudo ajuda a compreender a associação dos receptores de leptina e adiponectina com parâmetros clinicopatológicos. Objetivo: Correlacionar os diversos parâmetros clinicopatológicos com a expressão tecidual dos receptores de leptina e adiponectina no CCR. Métodos: Trata-se de um estudo transversal, prospectivo, realizado em um hospital terciário. Blocos de parafina fixados em formalina de todos os casos de CCR de ressecção radical foram coletados e a imuno-histoquímica (IHQ) foi realizada no tecido tumoral para receptor de leptina e adiponectina. As características do tumor e os parâmetros clínicos foram coletados dos prontuários médicos do hospital. Foi utilizado o teste do coeficiente de correlação de Pearson. Resultados: A imunohistoquímica foi realizada em 60 casos de CCR. Correlação positiva significativa da leptina foi observada com tamanho e metástase linfonodal, estágio avançado e grau do tumor (P<0,01). Foi observada uma correlação significativa entre o receptor de adiponectina e o CCR em relação à idade, estágio, metástase linfonodal, metástase à distância e grau do tumor. Conclusão: A expressão positiva de leptina e a expressão negativa de receptores de adiponectina no CCR ajudam a prever o risco de metástase.

Cytotoxicity based screening for radioprotective properties of methanolic extract of Tragia involucrata L. on cultured human peripheral lymphocytes exposed to gamma radiation

Radioprotective drugs of plant origin with bioactives are a boon against ionizing radiation injuries. Tragia involucrata L. (Indian stinging nettle), has medicinal properties and is traditionally used to treat various ailments. Here, we evaluated the radioprotective efficacy of the methanolic whole plant extract of T. involucrata against the damaging effects of gamma radiation. Cultured lymphocytes were treated with methanolic extract for one hour and irradiated with (1-4 Gy) gamma radiation. This pretreatment of lymphocytes with methanolic extract significantly increased the cell viability at 10 μg/mL and reduced the damage to the treated cells compared to the radiation control. In addition, a significant decrease in comet parameters (Comet length and percent DNA in tail and olive moment) and formation of micronuclei (P <0.001) were observed. It also decreased the levels of malondialdehyde, while regulating the status of the total antioxidant capacity, superoxide dismutase, catalase, reduced glutathione, and glutathione transferase (P <0.05) when compared to the radiation control. Similarly, a decrease in caspase 3 cellular activity compared to the radiation control was observed. The results indicated the methanolic extract to be an effective radioprotector up to 4 Gy, by enhancing the antioxidant enzyme levels, scavenging the production of reactive oxygen species, reducing the damaging effects of radiation by increasing the DNA repair mechanism, and by inhibiting the mitochondrial apoptotic pathway. Therefore, methanolic extract of the Indian stinging nettle, Tragia involucrata L. has been proposed as a candidate with a radioprotective property, and further study on animal models would strengthen this claim

Clinical and Laboratory Evaluation of Patients with Fever with Thrombocytopenia.

Aims: To evaluate clinical profile of fever with thrombocytopenia. To identify the causes of fever with thrombocytopenia. To assess the clinical complications associated with fever and thrombocytopenia. Material and methods: This study was done on patients, who were admitted to Sir T. Hospital and Government Medical College, Bhavnagar, Gujarat. We prospectively collected a series of 100 patients with fever and thrombocytopenia. Results: Age and sex distribution; In this study male out numbered female. Platelet count and bleeding; Of 100 patients four had bleeding manifestations. There is no correlation between platelet count and bleeding. Degree of thrombocytopenia in various diseases; (1) Viremia; Among infectious cases viremia including dengue accounted for the vast majority. In this study out of 100 cases viremia including dengue accounts for 52 cases. (2) Dengue; In our study dengue caused severe thrombocytopenia. Twenty patients out of 40 cases had count <50,000/mm3. (3) Malaria; In our study malaria caused mild-to-moderate thrombocytopenia with counts remaining between 50,000 to 1 lacs in most cases. Bleeding manifestations; In our study, out of 100 patients only four patients presented with bleeding manifestations. Three patients of mixed Plasmodium vivax with Plasmodium falciparum malaria presented with petechie, purpura and hematuria. One patient of dengue presented with gum bleeding. Platelet count and fever; In this study, shortest duration of fever is three days and longest is 10 days. Platelet count started increasing from 2nd day of admission to 8th day of admission with relative treatment. Enteric fever; In our study out of 100 patients three had fever with thrombocytopenia without any bleeding manifestations.

Glucose Tolerance in Nondiabetic Patients after First Attack of Acute Myocardial Infarction and its Outcome.

Aims: To find out the incidence of impaired glucose tolerance (IGT) and frank diabetes mellitus (DM) in patients of acute myocardial infarction (AMI) and to study the natural history of IGT in relation to AMI. Study Design: A crosssectional study was done in 60 patients of AMI in whom oral glucose tolerance test (OGTT) was performed after admission. Those with normal glucose tolerance on admission and till discharge were included in the study. Material and Methods: The study was conducted at the intensive coronary care unit (ICCU) of Shri Sayajirao General (SSG) Hospital, Vadodara, Gujarat. The study was done over a period of seven months in 60 patients of AMI. Results: The present study revealed that cardiovascular complications related to AMI were more common in patients with abnormal glucose tolerance. Conclusion: Glucometabolic abnormalities in nondiabetic patients with acute coronary event have an influence on in-hospital and short-term cardiovascular morbidity as well as mortality.

Solubility Enhancement and Formulation of Mouth Dissolving Tablet of Clonazepam with Solid Dispersion Technology

Clonazepam (CLZ) is an anticonvulsant benzodiazepine widely used in the treatment of epilepsy. CLZ is a BCS Class II drug and its bioavailability is thus dissolution limited. The objective of the present study was to prepare solid dispersions (SDs) of CLZ by various techniques, using the amphiphilic carrier Gelucire 50/13 in various proportions, to increase its water solubility. Drug-polymer interactions were investigated by Fourier-transform infrared (FTIR) and Ultra-Violet (UV) spectroscopy. The SDs were characterized physically by differential scanning calorimetry (DSC) and X-ray diffraction (XRD). A phase solubility study was performed and the stability constant (Ks) was found to be 275.27, while the negative Gibbs free energy (?Gotr) indicated spontaneous solubilization of the drug. The dissolution study showed that the SDs considerably enhanced the dissolution rate of the drug. The FTIR and UV spectra revealed no chemical incompatibility between the drug and Gelucire 50/13. XRD patterns and the DSC profiles indicated the CLZ was in the amorphous form, which explains the improved dissolution rate of the drug from its SDs. Finally, mouth dissolving tablets (MDTs) were prepared from the optimized batches (kneading method) of solid dispersion, using crospovidone and Doshion P544 resin as superdisintegrants. The tablets were characterized by in-vitro disintegration and dissolution tests. The study of the MDTs showed disintegration times in the range 32.0±0.85 to 20.0±1.30 sec and dissolution was faster than for the commercial preparation. In conclusion, this investigation demonstrated the potential of solid dispersions of a drug with Gelucire 50/13 for promoting the dissolution of the drug and contributed to the understanding of the effect of a superdisintegrant on mouth dissolving tablets containing a solid dispersion of a hydrophobic drug.

Primary neuroendocrine carcinoma presenting as mesenteric cyst.

Primary neuroendocrine carcinoma occurring in the mesentery is extremely rare. Surgical resection is the best treatment modality, with a chance of cure. We present a 65-year-old man with large mesenteric cyst and absence of bowel involvement. Histology showed a well-differentiated neuroendocrine tumor.

Cefuroxime axetil in the treatment of Salmonella typhi infection (enteric fever) in adults.

A study to evaluate the efficacy and safety of Cefuroxime Axetil in enteric fever was carried out in 30 adult hospitalised patients of either sex. A positive blood culture for S. typhi and sensitivity to cefuroxime axetil were confirmed prior to treatment. On admission, the baseline signs and symptoms were recorded and treatment initiated with cefuroxime axetil in a dose of 500 mg bd; which was continued for 7 days after normalization of temperature. The various clinical parameters were followed up daily during the treatment period and discharge permitted on normalization of temperature. Blood culture for S. typhi was repeated 3 days after stopping treatment. Follow-up Widal, stool and urine cultures were done wherever possible to check for relapse or carrier state. All the patients responded clinically to treatment and had bacteriologically negative blood cultures by the end of 14 days treatment. 87% of the patients responded within 7 days of treatment of which 60% were graded as Excellent responders as they responded within 4 days itself; while 13% took a longer time to respond. There were no relapses or carrier state as indicated by negative follow-up stool cultures. Only one patient reported a side-effect of mild headache confirming the safety of the drug. We conclude that Cefuroxime axetil in a dose of 500 mg bd is an effective and safe drug in the treatment of multi drug resistant enteric fever.

Smoking and hypertension: Indian scenario.

In a large multicentre study of 918 hypertensive patients, 28% of subjects were found to be smokers. Smokers had a higher average weight and associated diseases like coronary artery disease and diabetes. It is suggested that higher incidence of coronary artery disease and diabetes in the hypertensive smokers carries a higher risk of further cardiovascular events.