A case of primary amenorrhea with 46+XY genotype from Kashmir Valley

Primary amenorrhea is one of the common reproductive disorder affecting females. It leads to the absence of menarche in the reproductive age group in females and/or complete absence of reproductive organs. There are many causes which lead to PA, including genetic aberrations which are the leading factors.     

Utility of Dexrazoxane for the Attenuation of Epirubicin-Induced Genetic Alterations in Mouse Germ Cells

Dexrazoxane has been approved to treat anthracycline-induced cardiomyopathy and extravasation. However, the effect of dexrazoxane on epirubicin-induced genetic alterations in germ cells has not yet been reported. Thus, the aim of this study was to determine whether dexrazoxane modulates epirubicin-induced genetic damage in the germ cells of male mice. Our results show that dexrazoxane was not genotoxic at the tested doses. Furthermore, it protected mouse germ cells against epirubicin-induced genetic alterations as detected by the reduction in disomic and diploid sperm, spermatogonial chromosomal aberrations, and abnormal sperm heads. The attenuating effect of dexrazoxane was greater at higher dose, indicating a dose-dependent effect. Moreover, sperm motility and count were ameliorated by dexrazoxane pretreatment. Epirubicin induced marked biochemical changes characteristic of oxidative DNA damage including elevated 8-hydroxy-2ʹ-deoxyguanosine levels and reduction in reduced glutathione. Pretreatment of mice with dexrazoxane before epirubicin challenge restored these altered endpoints. We conclude that dexrazoxane may efficiently mitigate the epirubicin insult in male germ cells, and prevent the enhanced risk of abnormal reproductive outcomes and associated health risks. Thus, pretreating patients with dexrazoxane prior to epirubicin may efficiently preserve not only sperm quality but also prevent the transmission of genetic damage to future generations.     

Assessment of platelet function in patients with stroke using multiple electrode platelet aggregometry: a prospective observational study

The Qatari law, as in many other countries, uses brain death as the main criteria for organ donation and cessation of medical support. By contrast, most of the public in Qatar do not agree with the limitation or withdrawal of medical care until the time of cardiac death. The current study aims to examine the duration of somatic survival after brain death, organ donation rate in brain-dead patients as well as review the underlying etiologies and level of support provided in the state of Qatar. This is a retrospective study of all patients diagnosed with brain death over a 10-year period conducted at the largest tertiary center in Qatar (Hamad General Hospital). Among the 53 patients who were diagnosed with brain death during the study period, the median and mean somatic survivals of brain-dead patients in the current study were 3 and 4.5 days respectively. The most common etiology was intracranial hemorrhage (45.3%) followed by ischemic stroke (17%). Ischemic stroke patients had a median survival of 11 days. Organ donation was accepted by only two families (6.6%) of the 30 brain dead patients deemed suitable for organ donation. The average somatic survival of brain-dead patients is less than one week irrespective of supportive measures provided. Organ donation rate was extremely low among brain-dead patients in Qatar. Improved public education may lead to significant improvement in resource utilization as well as organ transplant donors and should be a major target area of future health care policies.     

The structure of arylamine N-acetyltransferase from Mycobacterium smegmatis--an enzyme which inactivates the anti-tubercular drug,isoniazid

Arylamine N-acetyltransferases which acetylate and inactivate isoniazid, an anti-tubercular drug, are found in mycobacteria including Mycobacterium smegmatis and Mycobacterium tuberculosis. We have solved the structure of arylamine N-acetyltransferase from M. smegmatis at a resolution of 1.7 A as a model for the highly homologous NAT from M. tuberculosis. The fold closely resembles that of NAT from Salmonella typhimurium, with a common catalytic triad and domain structure that is similar to certain cysteine proteases. The detailed geometry of the catalytic triad is typical of enzymes which use primary alcohols or thiols as activated nucleophiles. Thermal mobility and structural variations identify parts of NAT which might undergo conformational changes during catalysis. Sequence conservation among eubacterial NATs is restricted to structural residues of the protein core, as well as the active site and a hinge that connects the first two domains of the NAT structure. The structure of M. smegmatis NAT provides a template for modelling the structure of the M. tuberculosis enzyme and for structure-based ligand design as an approach to designing anti-TB drugs.     

Antigen-specific CD8+ T cell clonal expansions develop from memory T cell pools established by acute respiratory virus infections

Increasing age is associated with the development of CD8+ T cell clonal expansions (TCE) that can dominate the peripheral T cell repertoire and interfere with immune responses to infection and vaccination. Some TCE are driven by chronic infections, consistent with dysregulated outgrowth of T cell clones in response to persistent antigenic stimulation. However, a second class of TCE develops with age in the absence of chronic infections and is poorly understood in terms of origin or Ag dependence. In this study, we present evidence that Ag-specific TCE develop at high frequencies from conventional memory CD8+ T cell pools elicited by nonpersistent influenza and parainfluenza virus infections. Putative TCE occurred in both the central- and effector-memory CD8+ T cell populations and did not require Ag for their maintenance. In addition, they were similar to normal memory T cells in terms of phenotype and function, suggesting that they develop stochastically from the memory T cell pool. These data suggest that memory T cell pools become progressively dysregulated over time and this may have a significant impact on immune responsiveness in the aged.     

Identification of QTLs for Yield and Associated Traits in F₂ Population of Rice

Identification of quantitative trait loci (QTLs) controlling yield and yield-related traits in rice was performed in the F₂ mapping population derived from parental rice genotypes DHMAS and K343. A total of 30 QTLs governing nine different traits were identified using the composite interval mapping (CIM) method. Four QTLs were mapped for number of tillers per plant on chromosomes 1 (2 QTLs), 2 and 3; three QTLs for panicle number per plant on chromosomes 1 (2 QTLs) and 3; four QTLs for plant height on chromosomes 2, 4, 5 and 6; one QTL for spikelet density on chromosome 5; four QTLs for spikelet fertility percentage (SFP) on chromosomes 2, 3 and 5 (2 QTLs); two QTLs for grain length on chromosomes 1 and 8; three QTLs for grain width on chromosomes1, 3 and 8; three QTLs for 1000-grain weight (TGW) on chromosomes 1, 4 and 8 and six QTLs for yield per plant (YPP) on chromosomes 2 (3 QTLs), 4, 6 and 8. Most of the QTLs were detected on chromosome 2, so further studies on chromosome 2 could help unlock some new chapters of QTL for this cross of rice variety. Identified QTLs elucidating high phenotypic variance can be used for marker-assisted selection (MAS) breeding. Further, the exploitation of information regarding molecular markers tightly linked to QTLs governing these traits will facilitate future crop improvement strategies in rice.     

Efficient short-term control of hypercortisolaemia by low-dose etomidate in severe paediatric Cushing's disease

BACKGROUND: Paediatric Cushing's disease (CD) is rare, but is associated with considerable morbidity and requires effective treatment. Control of hypercortisolaemia is recommended prior to definitive therapy by transsphenoidal pituitary surgery with selective adenomectomy. We describe a 6.2-year-old male with severe hypercortisolaemia and life-threatening complications of Cushing's disease. Control of cortisol with metyrapone and ketoconazole was ineffective, and due to his deteriorating condition, the decision was taken to proceed to bilateral adrenalectomy. METHODS: Low-dose IV infusion of etomidate, with dose titration according to serum cortisol levels, was administered. RESULTS: Etomidate infusion (3.0 mg/h i.v.) decreased serum cortisol from 1,250 to 250 nmol/l within 24 h. Combined etomidate and hydrocortisone therapy was maintained to provide stable serum cortisol levels within the desired range for 12 days prior to successful bilateral adrenalectomy. CONCLUSION: In our experience, etomidate was effective and safe for short-term control of severe hypercortisolaemia in a severely ill child.     

Lack of fitness costs associated with acetamiprid resistance in Bemisia tabaci (Hemiptera: Aleyrodidae)

Sweetpotato whitefly, Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae), is a devastating pest that can cause severe damage to a range of crops by direct feeding and by plant virus transmission. Because of indiscriminate use of insecticides, this whitefly has developed resistance to several insecticides, including neonicotinoids. Our objectives were to determine fitness components affected by acetamiprid resistance in B. tabaci. Assay results showed that selection with acetamiprid had removed heterozygotes from the field population because the survival rate of the resistant population was significantly greater than that of the field population at a very high dose. Comparison of various life traits between the acetamiprid-selected (Aceta-SEL) population and three other populations showed that the numbers of eggs laid by acetamiprid Aceta-SEL population were significantly lower compared with that of other populations but that the proportions of eggs hatched were significantly higher. However, the time taken by nymphal stages of the Aceta-SEL population to develop was significantly higher than that of the susceptible populations. The intrinsic rate of increase, net reproductive rate, mean generation time, and doubling time of Aceta-SEL was significantly higher than Lab-PK and UNSEL populations, but the growth index was similar for all populations. The growth index and high intrinsic value of Aceta-SEL population suggest that the resistance allele may not have detrimental impact. The lack of fitness costs in B. tabaci could promote the rapid development of resistance to acetamiprid and other neonicotinoids. This resistance could threaten the sustainability of whitefly management program on genetically engineered cotton (Gossypium hirsutum L.) where neonicotinoids are being sprayed to manage sucking pests in the field.     

GSTP1 I105V polymorphism and susceptibility to colorectal cancer in Kashmiri population

The glutathione S-transferase (GST) enzyme encoded by the GSTP1 gene is one of the critical enzymes involved in detoxification of carcinogens. The substitution of isoleucine to valine residue at position 105 of the GSTP1 protein results in decreased enzyme activity and hence less capability of effective detoxification. Hence, we investigated the role of GSTP1 I105V polymorphism in modulating the risk of colorectal cancer (CRC) associated in a Kashmiri population. We designed a case-control study in which 86 CRC cases were studied for GSTP1 I105V polymorphism against 160 controls taken from the general population employing the polymerase chain reaction-restriction length fragment polymorphism technique. There was no significant association between GSTP1 I105V genotypes and the disease, but the Val/Val genotype was associated with an increased risk with some clinicopathological parameters (odds ratio=1.5; 95% confidence interval=0.55-4.57). This study suggests that the GSTP1 I105V polymorphism may modulate CRC risk in the Kashmiri population.