Role of nitric oxide in the biology, physiology and pathophysiology of reproduction

Following its benchmark discovery, nitric oxide (NO) is nowknown to play important functional roles in a variety of physiologicalsystems. Within the vasculature, NO induces vasodilation, inhibitsplatelet aggregation, prevents neutrophil/platelet adhesionto endothelial cells, inhibits smooth muscle cell proliferationand migration, regulates programmed cell death (apoptosis) andmaintains endothelial cell barrier function. NO generated byneurons acts as a neurotransmitter, whereas NO generated bymacrophages in response to invading microbes acts as an antimicrobialagent. Because neurons, blood vessels and cells of the immunesystem are integral parts of the reproductive organs, and inview of the important functional role that NO plays in thosesystems, it is likely that NO is an important regulator of thebiology and physiology of the reproductive system. Indeed, inthe past 10 years, NO has established itself as a polyvalentmolecule which plays a decisive role in regulating multiplefunctions within the female as well as the male reproductivesystem. This review provides an overview of the role of NO invarious reproductive organs under physiological and pathologicalconditions.     

Comparative analysis of the polycystic kidney disease 1 (PKD1) gene reveals an integral membrane glycoprotein with multiple evolutionary conserved domains

PKD1 is the major locus of the common genetic disorder autosomal dominant polycystic kidney disease (ADPKD). Analysis of the predicted protein sequence of the human PKD1 gene, polycystin, shows a large molecule with a unique arrangement of extracellular domains and multiple putative transmembrane regions. The precise function of polycystin remains unclear with a paucity of mutations to define key structural and functional domains. To refine the structure of this protein we have cloned the genomic region encoding the Fugu PKD1 gene. Fugu PKD1 spans 36 kb of genomic DNA and has greater complexity with 54 exons compared with 46 in man. Comparative analysis of the predicted protein sequences shows a lower level of homology than in similar studies with identity of 40 and 59% similarity. However key structural motifs including leucine rich repeats (LRR), a C-type lectin and LDL-A like domains and 16 PKD repeats are maintained. A region of homology with the sea urchin REJ protein was also confirmed in Fugu but found to extend over 1000 amino acids. Several highly conserved intra- and extra- cellular regions, with no known sequence homologies, that are likely to be of functional importance were detected. The likely structure of the membrane associated region has been refined with similarity to the PKD2 protein and voltage gated Ca2+ and Na+ channels highlighted over part of this area. The overall protein structure has therefore been clarified and this comparative analysis derived structure will form the basis for the functional study of polycystin and its individual domains.      

RENAL TRANSPLANTATION – AN EARLY EXPERIENCE

Renal transplant (RT) is now a therapy of choice for end stage renal disease (ESRD). The Nephrology Unit, Asvini started functioning in Dec 90 and to date 1298 sittings of hemodialysis have been given to 45 patients. Of these, 35 were in ESRD and 11 patients underwent renal transplantation at this hospital during the period Jan 91 – Dec 93. One patient expired after 18 months of transplantation due to infection. Early experience in screening patients for RT, use of immunosuppression, management of rejection episodes and protocol are presented with special emphasis on its relevance to the Armed Forces.KEY WORDS: Transplantation, Renal Failure, Immunosuppression, Rejection     

SCREENING PROCEDURES IN PEDIATRICS

Pediatric health screening procedures, both prenatal and postnatal, have a tremendous potential in improving the health status of children and in turn reducing the resource burden on the parents and the State. The existing recommendations, inherent problems and different screening procedures are discussed. The need for suitable mass screening pediatric procedures in the Indian context is stressed.KEY WORDS: Pediatric screening procedures     

Soft-tissue sarcomas of the limbs at high risk of malignity. Current role of surgery and conservative treatment]

The authors discuss the role of surgical treatment in patients with highly malignant soft tissue sarcomas in the limbs. A careful analysis is made of different therapies on the basis of the results obtained by the authors and those reported in the literature. The anatomic classification of lesions is based on functional anatomic compartments, defined as intra- or extracompartmental. If a lesion was within an intrafascial compartment, all the muscles with intact fascial sheaths have up till now been removed "en bloc" to obtain radical margins. Many authors now think that all manifest disease be removed with a generous soft tissue margin on all sides to ensure adequate local treatment. Amputation has commonly been performed for extracompartmental lesions, but a multinodal treatment programme, including limb-sparing resection and tumour-bed radiation, should now be considered if possible in the management of these tumours.     

Toxic cardiogenic shock in a patient receiving weekly 24-h infusion of high-dose 5-fluorouracil and leucovorin

A 54-year-old man was treated with weekly 24-h infusion of high-dose 5-fluorouracil (2600 mg/m2) and leucovorin (100 mg/m2) for metastatic colon cancer. At first, he tolerated the treatment well and no significant toxicity was identified. After a total of eight courses of treatment, a stable disease was observed, but mild shortness of breath was found on occasion. The patient had no previous history of cardiac disease and the heart performance assessed by left ventricular ejection fraction before treatment was normal. Unfortunately, acute pulmonary edema with lethal cardiogenic shock occurred during the ninth course of treatment, in spite of intensive medical treatment. The chest X-ray showed extreme cardiomegaly. Repeated assessment of his heart function by echocardiogram and ventricular ejection fraction revealed a very poor cardiac performance. Toxic cardiogenic shock during weekly 24-h infusion of high-dose 5-fluorouracil and leucovorin is extremely rare. To the best of our knowledge, no case has been reported in the English literature. We report a case and the relevant literature about the incidence, clinical picture and possible pathophysiology on 5-fluorouracil-related cardioxicity is reviewed.      

阿魏酸钠对乙醇所致小鼠肝脏抗氧化功能改变的拮抗作用

研究了不同剂量乙醇对小鼠抗氧化和解毒功能的影响以及阿魏酸钠的拮抗作用。结果表明,大剂量乙醇(11.4g·kg^-1ig)引起肝脏GSH-Px活性升高的同时,肝脏GSH-Re,SOD和GST活性降低,GSH耗竭,而血清GST升高;阿魏酸钠(100mg·kg^-1ig,qd×10)预处理则明显拮抗大剂量乙醇所致的上述改变。表明阿魏酸钠对急性乙醇所致肝损害具有良好保护作用,其机理可能与提高GSH氧化还原酶功能、增加SOD活性和增强GSH结合反应有关。研究结果还提示,血清GST水平是反映乙醇性肝损害的灵敏指标。