Alterations in hepatic microsomal mixed-function oxidase system during different levels of food restriction in adult male and female rats

Wistar strain adult male and female rats were given 25, 50 and 75% less food than an ad libitum-fed group of rats for 45 d and the effects of food restriction on hepatic drug metabolizing enzymes, microsomal electron transport components, NADPH-dependent lipid peroxidation and glutathione-S-transferase activities were studied. Compared to ad libitum-fed controls, the cytochrome P-450 levels were higher in food restricted male rats, while they were lower in food restricted females. The activities of NADPH cytochrome c reductase were lower in food restricted females than in ad libitum-fed controls. The activities of drug metabolizing enzymes, aminopyrine N-demethylase and acetanilide hydroxylase were higher in food restricted males, whereas in food restricted females these activities were lower than in respective groups fed ad libitum. Microsomal, NADPH-dependent lipid peroxidation was higher in 25 and 50% food restricted females while in 50 and 75% food restricted males it was lower than in ad libitum controls of the same sex. The cytosolic glutathione-S-transferase activities were lower in food restricted rats of both the sexes than in the same sexed controls. Another group of male and female rats were given 75% less food than the ad libitum-fed rats and refed for 3 d prior to killing. Here also, the effects of restriction were different between sexes. It is concluded that hepatic microsomal mixed-function oxidase system (MFOS) is altered due to feed restriction and food restriction followed by refeeding, in a sex-related manner.     

Hearing acuity in post spinal analgesia period

100 cases of either sex 96 males and 4 females in their mean age group of 45 year ± 14.51 standard deviation were selected for this study to analyse the Hearing Acuity in the post spinal analgesia period during a period of eight months in the E.N.T department of the J.N. Medical College A.M.U. Aligarh. The size of the needle used for spinal analgesia was 22G and the equipment for Audiometry was the pure tone Audiometer. Pure tone Audiometry was done pre-operatively and then on the 1st, 3rd, 5th and 12th subsequent post-operative days and then after six months. It was found that 12% of the patients showed incidence of mild hearing loss. However, the loss was transient, reversible, within low frequency range (250, 500, 1000 Hz), and no patient suffered from any permanent hearing loss.     

Prophylaxis in RSV infection (Palivizumab)--is it worthwhile?

Respiratory syncytial virus (RSV) is a recognised cause of lower respiratory tract infection in infants and young children. It causes severe respiratory disease in preterm infants with or without chronic lung disease. This study, conducted at Waterford Regional Hospital, evaluates the incidence of RSV infection in hospitalised children, its seasonal variation, and effectiveness of its prevention. Thirty eight percent of admitted children with bronchiolitis were RSV positive in the year 1999 November to March is the peak season for this infection. A highly selected group of 7 preterm children with or without chronic lung disease received Palivizumab prophylaxis. Not one of them acquired RSV infection. The high cost of Palivizumab was the main factor for its restricted use. Palivizumab was found to be effective in preventing RSV infection in our study. Since we had a small number of patients, further studies are needed for its economic and judicious use. Respiratory syncytial virus (RSV) is virulent easily transmissible and the most common cause of lower respiratory tract disease in children of less than 2 years of age. Up to 98% of children attending day care will be infected in single RSV season. Between 0.5% and 3.2% of children with RSV infection require Hospitalisation. Approximately 90,000 hospital admissions and 4500 deaths per year were reported in United States. In Ireland 2807 patients were admitted with Bronchiolitis in 1998. Major risk factors for hospitalisation due to RSV are Prematurity, chronic lung disease, congenital heart disease, compromised immunity and age younger then 6 weeks in otherwise healthy children. No effective treatment of RSV positive bronchiolitis beside supportive care in the form of adequate nutrition and oxygen therapy is available. Antiviral therapies such as Ribavirin has not been proved to be effective in RSV infection. Bronchodilators show variable results. Corticosteroids were not found effective. There is no effective vaccine available as yet. There is no proven method for active immunity. Various immunoglobulins are available for acquiring passive immunity against RSV infection. PREVENT study group in Jan. 1997 showed intravenous immunoglobulin (RSV- IGIV) use in reducing 41% to 63% hospitalisation in RSV patients. But RSV-IGIV was not licensed outside the United States because of risk of transmission of blood borne products, difficulty in administration ie. intravenous access, large fluid volume (15 ml/kg), high protein load (750 mg/kg), shortage of supply and need to postpone live vaccine (eg. MMR, varicella). monoclonal antibody Palivizumab was developed for prophylaxis against RSV infection. Clinical safety and efficacy of Palivizumab were demonstrated in IMpact trial published in Sept. 1998. Reduction in hospitalisation up to 55% was noted in this study. It was a pivotal randomised, double blind, placebo controlled phase 3 study conducted in 139 centres throughout Canada, United States and United Kingdom. We looked at our experience in patients admitted with bronchiolitis in Waterford Regional Hospital. We described the outcome of carefully selected Seven children of high risk group for Palivizumab prophylaxis. Its clinical Implications and cost effectiveness was evaluated in this study.     

PSTPIP1‐associated myeloid‐related proteinemia inflammatory syndrome: A rare cause of childhood neutropenia associated with systemic inflammation and hyperzincemia

Neutropenia in pediatric patients can be due to a variety of disorders. We describe two patients who underwent extensive evaluation over many years for arthralgias and moderate neutropenia of unclear etiology. Genetic testing identified a pathogenic variant in PSTPIP1 (proline‐serine‐threonine phosphatase‐interacting protein 1) in both patients. Markedly elevated inflammatory markers and zinc levels confirmed the rare diagnosis of PSTPIP1‐associated myeloid‐related proteinemia inflammatory (PAMI) syndrome, tailoring treatment. Neutropenia is common in patients with PAMI syndrome. Unique mutations seen in PAMI syndrome may account for the specific phenotypic features of this disorder.     

Whole exome sequencing identified a novel single base pair insertion mutation in the EYS gene in a six generation family with retinitis pigmentosa

Retinitis pigmentosa (RP) is a group of inherited progressive retinal dystrophies (RD) and is characterized by photoreceptor degeneration. RP is clinically and genetically heterogeneous disorder. More than 70 genes are known and, thus, identification of causative genes and mutations in known genes is challenging. This study was designed to identify the underlying genetic defect in a large extended Saudi family with multiple RP affected members. Fundus photography, Optical Coherence Tomography (OCT) and visual field perimetry were performed for affected individuals. Whole exome sequencing was used to detect the underlying genetic defect in a large family with 12 affected individuals showing autosomal recessive isolated RP. WES data analysis identified a novel insertion mutation in the EYS (eyes shut homolog) gene (c.910_911insT; p.Trp304LeufsTer8). Sanger sequencing validates the variant discovered through exome in all 12 affected individuals and showed that this mutation is segregating with RP phenotype in an autosomal recessive manner in 51 individuals of the family tested here. Our study expands the mutation spectrum of EYS gene in RP patients and extends the body of evidence that supports the importance of EYS gene in eye development.     

The Achilles’ heel of cancer survivors: fundamentals of accelerated cellular senescence

Recent improvements in cancer treatment have increased the lifespan of pediatric and adult cancer survivors. However, cancer treatments accelerate aging in survivors, which manifests clinically as the premature onset of chronic diseases, such as endocrinopathies, osteoporosis, cardiac dysfunction, subsequent cancers, and geriatric syndromes of frailty, among others. Therefore, cancer treatment–induced early aging accounts for significant morbidity, mortality, and health expenditures among cancer survivors. One major mechanism driving this accelerated aging is cellular senescence; cancer treatments induce cellular senescence in tumor cells and in normal, nontumor tissue, thereby helping mediate the onset of several chronic diseases. Studies on clinical monitoring and therapeutic targeting of cellular senescence have made considerable progress in recent years. Large-scale clinical trials are currently evaluating senotherapeutic drugs, which inhibit or eliminate senescent cells to ameliorate cancer treatment–related aging. In this article, we survey the recent literature on phenotypes and mechanisms of aging in cancer survivors and provide an up-to-date review of the major preclinical and translational evidence on cellular senescence as a mechanism of accelerated aging in cancer survivors, as well as insight into the potential of senotherapeutic drugs. However, only with time will the clinical effect of senotherapies on cancer survivors be visible.

Cancer survival times have increased annually owing to advances in early detection and treatment that prolong patient survival. However, increasing survivorship has underscored the observation that cancer survivors develop age-related diseases prematurely, which cause significant morbidity, health expenditures, and mortality. Many cancer survivors have been exposed to chemotherapy, radiotherapy, or both; despite eradicating cancer cells, these therapies also damage normal cells to accelerate biologic aging, such that a discrepancy exists between their biologic and chronologic age (1). Considerable data exist regarding the phenotypes of accelerated aging. However, mechanical and molecular uncertainties have limited the study of these manifestations in a clinical context. Our Review discusses accelerated aging phenotypes in cancer survivors and the cellular mechanisms underpinning these phenomena. We then discuss the translational evidence on how accelerated aging phenotypes, mainly related to senescence, are being targeted while highlighting areas of uncertainty for future research to address.     

Challenges and opportunities of utilizing municipal solid waste as alternative building materials for sustainable development goals: A review

Strict environmental concern, depletion, and price hike of building construction materials are driving scientific studies for the search of alternative materials for building construction. To this end sustainable building materials could be a fruitful solution. This review aims to discern the environmental efficacy of solid waste management (SWM) and its relationship with four stimuli i.e., economic structure, regulatory structure, science, and time. The study also highlights the investigation of governance network to figure out the regulatory structure and governance of waste management. Extensive details on solid waste with their sources, recycling potential and their current utilization for substantial development are outlined. A throughout of the production process, properties, advantages, disadvantages, and the global economy of building material developed through recycling of solid waste are discussed. This article also deals with the sustainability, social, and environmental impact of green building materials. The study identifies the future direction for the effective utilization of solid waste for developing building materials. Further, the scope of the present also focusses on the concept of circular economy for developing construction materials through recycling of solid waste, which provides an easy reference for solid waste processing towards sustainability.