Epigenetic factors Polycomb (<Emphasis Type="Italic">Pc</Emphasis>) and Suppressor of zeste (<Emphasis Type="Italic">Su</Emphasis>(<Emphasis Type="Italic">z</Emphasis>)2) negatively regulate longevity in <Emphasis Type="Italic">Drosophila melanogaster</Emphasis>

The process of aging is a hallmark of the natural life span of all organisms and individuals within a population show variability in the measures of age related performance. Longevity and the rate of aging are influenced by several factors such as genetics, nutrition, stress, and environment. Many studies have focused on the genes that impact aging and there is increasing evidence that epigenetic factors regulate these genes to control life span. Polycomb (PcG) and trithorax (trxG) protein complexes maintain the expression profiles of developmentally important genes and regulate many cellular processes. Here, we report that mutations of PcG and trxG members affect the process of aging in Drosophila melanogaster, with perturbations mostly associated with retardation in aging. We find that mutations in polycomb repressive complex (PRC1) components Pc and Su(z)2 increase fly survival. Using an inducible UAS-GAL4 system, we show that this effect is tissue-specific; knockdown in fat body, but not in muscle or brain tissues, enhances life span. We hypothesize that these two proteins influence life span via pathways independent of their PRC1 functions, with distinct effects on response to oxidative stress. Our observations highlight the role of global epigenetic regulators in determining life span.     

Case report: Acute hepatitis E infection with coexistent glucose-6-phosphate dehydrogenase deficiency

Hepatitis E virus is one of the leading causes of acute viral hepatitis in India but usually manifests as a mild self-limiting illness. Viral hepatitis in the presence of glucose-6-phosphate dehydrogenase (G6PD) deficiency may be associated with complications such as severe anemia, hemolysis, renal failure, hepatic encephalopathy and even death. The incidence of G6PD deficiency in the general population of northern India is reported to be between 2.2% and 14%. Despite both hepatitis E infection and G6PD deficiency being common, their impact on patient illness has only recently been reported. The present study reports a case of severe hemolysis in a patient with G6PD deficiency and hepatitis E infection. Key Words: Glucose-6-phosphate dehydrogenase, G6PD, Hemolysis, Hepatitis EHepatitis E is an enterically transmitted virus and is one of the most common causes of acute viral hepatitis in India (1). Glucose-6-phosphate dehydrogenase (G6PD) deficiency is found in 2.2% to 14% of the general population in North India (2). The coexistence of viral hepatitis and G6PD deficiency has been reported to be associated with severe jaundice and other complications (3,4). Hepatitis E infection with G6PD deficiency has been associated with more severe illness in only one previous report (5). We report an additional case.     

Alfuzosin attenuates erectile dysfunction in rats with partial bladder outlet obstruction

OBJECTIVE

To determine how partial bladder outlet obstruction (PBOO) in a rat model affects erectile function, and whether an uroselective α1‐adrenoceptor antagonist, alfuzosin (Sanofi‐Aventis, Paris, France) attenuates any erectile dysfunction (ED).

MATERIALS AND METHODS

Adult male Sprague‐Dawley rats (120) were randomized into four groups: 1, sham‐operated; 2, alfuzosin‐treated; 3, PBOO; and 4, alfuzosin‐treated with PBOO. Groups 3 and 4 were subjected to PBOO for 6 weeks by ligation of the urethra, while groups 2 and 4 rats received daily oral alfuzosin (10 mg/day) for 6 weeks. In vivo erectile responses were monitored by evaluating ratios of intracavernosal pressure (ICP)/mean arterial pressure, and total ICP (area under the curve). Organ‐bath studies were performed on corpus cavernosum smooth muscle (CCSM) strips. Nitric oxide synthase (NOS) expression was determined immunohistochemically (IHC) for neuronal (n)NOS and by Western blot analysis for endothelial (e) and inducible (i) NOS protein.

RESULTS

Rats with PBOO showed lower erectile responses than controls. Maximum electrical field stimulation‐mediated and endothelium‐dependent acetylcholine‐induced relaxations and contractile responses to phenylephrine were significantly reduced in CCSM strips from the PBOO group. The NO donor sodium nitroprusside completely relaxed CCSM from rats in all groups. IHC analyses showed decreased expression of nNOS in PBOO groups compared with controls; by contrast, protein expression of eNOS and iNOS was increased. Alfuzosin‐treatment partially attenuated functional and molecular changes in penises of PBOO rats.

CONCLUSION

Rats with PBOO show ED, most likely due to altered NOS expression and NO bioavailability. The α‐adrenoreceptor antagonist alfuzosin reversed this ED by altering sympathetic tone, increasing NO‐induced relaxation and augmenting blood flow in the penis. This study suggests a rationale for further clinical trials using combinations of α‐adrenoceptor antagonists and phosphodiesterase‐5 inhibitors in patients with ED and lower urinary tract symptoms.     

Induction of spindle cell morphology in human vascular endothelial cells by human herpesvirus 8-encoded viral FLICE inhibitory protein K13

Human herpesvirus 8 (HHV8), also known as Kaposi's sarcoma-associated herpesvirus, is linked to the development of Kaposi's sarcoma, a disease characterized by the presence of distinctive proliferating spindle-like cells. Although HHV8 can induce spindle cell transformation of vascular endothelial cells in vitro, the viral gene(s) responsible for this phenotype remain to be identified. We demonstrate that expression of HHV8-encoded viral Fas-associated death domain protein-like IL-1beta-converting enzyme inhibitory protein K13 is sufficient to induce spindle cell phenotype in human umbilical vein endothelial cells (HUVEC), which is associated with the activation of the nuclear factor-kappaB (NF-kappaB) pathway and can be blocked by Bay-11-7082, a specific inhibitor of this pathway. K13 induces the expression of several genes known to be upregulated in HHV8-transformed vascular endothelial cells, such as interleukin (IL)-6, IL-8, CXC ligand 3 (CXCL3), orphan G protein coupled receptor (RDC1), cyclooxygenase-2 (COX-2) and dual-specificity phosphatase 5 (DUSP5). Furthermore, similar to K13, HHV8-induced spindle cell transformation of HUVEC is associated with NF-kappaB activation and can be blocked by Bay-11-7082. Thus, ectopic expression of a single latent gene of HHV8 is sufficient for the acquisition of spindle cell phenotype by vascular endothelial cells and NF-kappaB activation plays an essential role in this process.     

Simultaneous occurrence of type I diabetes mellitus and juvenile rheumatoid arthritis

The association of juvenile rheumatoid arthritis and type 1 diabetes mellitus is rare. These two diseases belong to different clusters of autoimmune diseases and it is uncommon for diseases belonging to different cluster occurring together. This is a case report of a fourteen-year-old girl having the above two disorders along with autoimmune thyroid disease.