Mahmood Husain Qazi

Steroid levels in preovulatory and gravid lizards (Uromastix hardwicki).

Progesterone, testosterone, and estradiol-17β were measured by radioimmunoassay in the plasma and ovarian tissues of preovulatory and gravid spiny-tailed lizards (Uromastix hardwicki). Plasma titers of all three steroids were significantly higher in females carrying the oviductal eggs as compared to the values obtained in the preovulatory animals. Progesterone content of the corpora lutea present in the ovaries of gravid females was several times higher than the concentration of this hormone in the preovulatory follicular tissue. Testosterone and estradiol concentrations were also significantly higher in the luteal than in the follicular tissues. These data suggest that the rise in plasma levels of steroids during gravidity is mainly due to the steroidogenic activity of the corpus luteum and that the functions generally attributed to the reptilian luteal tissue may be mediated not only by progestins alone but also by other steroids synthesized by the corpus luteum in this reproductive phase.

Annual androgen rhythm in the spiny-tailed lizard, Uromastix hardwicki.

Abstract Monthly changes in plasma and testicular androgen concentrations of the spiny-tailed lizard, Uromastix hardwicki, were measured using a specific testosterone radioimmunoassay. A peak in plasma testosterone levels (22.4 ± 2.6 ng/ml) was associated with maximal testicular weights in late March, preceding the mating period in April. Simultaneous with testicular regression in May, there was a marked drop in plasma testosterone values. From June to January, plasma testosterone levels remained more or less uniform, and the mean monthly estimations made during this period ranged between 4.6 and 7.2 ng/ml. Plasma testosterone concentrations tended to increase again in February. Testicular testosterone concentrations, expressed per 100 mg of tissue, were low during the breeding period (March and April) and fell to minimal levels (3.1 ± 0.3 ng/100 mg) in the second week of May. In June, tissue testosterone levels began to rise, reaching a peak by late August or early September, just prior to the fall recrudescence of the testis. There was a marked fall in tissue testosterone levels during October and November and a more gradual decrease was recorded from January to May. Tissue testosterone content calculated per testis had two peaks, one coinciding with the recrudescent phase of the testis and the second larger peak coinciding with the breeding period when the testicular weights were maximal. Rise in relative as well as absolute testosterone concentrations, in late summer and fall, were not reflected in plasma testosterone levels. The androgen rhythm in this lizard is discussed in relation to changes in testicular weight and the spermatogenic cycle.

Recent Updates in the Treatment of Neurodegenerative Disorders Using Natural Compounds

Neurodegenerative diseases are characterized by protein aggregates and inflammation as well as oxidative stress in the central nervous system (CNS). Multiple biological processes are linked to neurodegenerative diseases such as depletion or insufficient synthesis of neurotransmitters, oxidative stress, abnormal ubiquitination. Furthermore, damaging of blood brain barrier (BBB) in the CNS also leads to various CNS-related diseases. Even though synthetic drugs are used for the management of Alzheimers disease, Parkinsons disease, autism, and many other chronic illnesses, they are not without side effects. The attentions of researchers have been inclined towards the phytochemicals, many of which have minimal side effects. Phytochemicals are promising therapeutic agents because many phytochemicals have anti-inflammatory, antioxidative as well as anticholinesterase activities. Various drugs of either synthetic or natural origin applied in the treatment of brain disorders need to cross the BBB before they can be used. This paper covers various researches related to phytochemicals used in the management of neurodegenerative disorders.

The role of epigenetics in personalized medicine: challenges and opportunities

Epigenetic alterations are considered to be very influential in both the normal and disease states of an organism. These alterations include methylation, acetylation, phosphorylation, and ubiquitylation of DNA and histone proteins (nucleosomes) as well as chromatin remodeling. Many diseases, such as cancers and neurodegenerative disorders, are often associated with epigenetic alterations. DNA methylation is one important modification that leads to disease. Standard therapies are given to patients; however, few patients respond to these drugs, because of various molecular alterations in their cells, which may be partially due to genetic heterogeneity and epigenetic alterations. To realize the promise of personalized medicine, both genetic and epigenetic diagnostic testing will be required. This review will discuss the advances that have been made as well as the challenges for the future.

Hepatoprotective Effects of Silybum marianum (Silymarin) and Glycyrrhiza glabra (Glycyrrhizin) in Combination: A Possible Synergy

Oxidative stress, lipid peroxidation, and transaminase reactions are some of the mechanisms that can lead to liver dysfunction. A time-dependent study was designed to evaluate the ability of silymarin (SLN) and glycyrrhizin (GLN) in different dosage regimens to lessen oxidative stress in the rats with hepatic injury caused by the hepatotoxin carbon tetrachloride. Wistar male albino rats (n = 60) were randomly assigned to six groups. Group A served as a positive control while groups B, C, D, E, and F received a dose of CCl4 (50% solution of CCl4 in liquid paraffin, 2 mL/kg, intraperitoneally) twice a week to induce hepatic injury. Additionally, the animals received SLN and GLN in different doses for a period of six weeks. CCl4 was found to induce hepatic injury by significantly increasing serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and thiobarbituric acid reactive substances while decreasing total protein and the activities of reduced glutathione, superoxide dismutase, and catalase. Treatment with various doses of SLN and GLN significantly reduced ALT, AST, ALP, and TBARS levels and increased GSH, SOD, and CAT levels. Our findings indicated that SLN and GLN have hepatoprotective effects against oxidative stress of the liver.

Characterization and androgen dependence of specific proteins in the epididymis of adult rhesus monkey (Macaca mulatta).

The androgen dependence and regional distribution of specific epididymal proteins have been investigated in the adult rhesus monkey (Macaca mulatta). The protein pattern of the epididymal cytosol was studied in intact, castrated, and testosterone-treated castrated monkeys by polyacrylamide gel electrophoresis (PAGE) and electrofocusing. At least five distinct protein components of the epididymal cytosol were androgen-sensitive. The PAGE of cytosol from various portions of the epididymis showed that whereas four protein components were uniformly distributed in the caput, corpus, and caudal segments, one of the androgen-dependent proteins was found to be associated with the caudal portion of the epididymis. Electrofocusing of epididymal cytosol also confirmed the presence of five androgen-dependent proteins in the adult monkey. The isoelectric points of these proteins were shown to range between 5.6 and 6.5, and the molecular weights were found to range between 15,000 and 61,000.

Effect of temperature and pregnant mare's serum gonadotropin on testicular function in the spiny-tailed lizard, Uromastix hardwicki☆

Abstract The effect of temperature and pregnant mares serum gonadotropin (PMSG) was observed on the testes of Uromastix hardwicki at a time of the year (November) when the seminiferous epithelium contained abundant proliferating spermatogonia and some primary spermatocytes. This recrudescent state of the testes was maintained by keeping the animals at 20° for 10 days. But, in lizards kept at 35°, there was a marked decrease in the testis weight. The seminiferous tubules were lined mostly with Sertoli cells and a few resting types of spermatogonia. The interstitial cells were only slightly affected and there was no reduction in androgen concentrations in the testicular tissue or plasma, as measured by testosterone radioimmunoassay. At 20°, injections of 20 IU of PMSG daily for 10 days induced an increase in the number of primary spermatocytes and production of spermatids in certain regions of the tubules. In the PMSG-treated lizards kept at 35° the testes contained a single layer of resting spermatogonia placed along the basement membrane. Under these conditions PMSG failed to maintain the active state of the seminiferous epithelium. Unlike the germinal cells, the interstitial cells were markedly stimulated by PMSG at 20 or 35°. Testicular and plasma androgen levels were increased severalfold in gonadotropin-treated lizards. The elevation of androgen levels as a result of PMSG stimulation was higher in lizards kept at 35°. It is suggested that in Uromastix hardwicki, the germinal epithelium responds differentially to PMSG treatment at the two different temperatures and that the activity of the interstitial cells is not inhibited by hyperthermia.

Current view from Alzheimer disease to type 2 diabetes mellitus.

Alzheimers disease (AD) is a neurodegenerative disorder that leads to memory problems. It has been associated with type 2 diabetes mellitus at both the molecular and biochemical level. Pancreatic cells have molecular similarities to the brain at the transcriptomic and proteomic levels. Several genes have been reported to be responsible for both AD and diabetes. Currently, no proper treatment is available but various therapeutic approaches are utilized worldwide for the management of these disorders and may be nanoparticles and herbal treatment of Bacopa monnieri will make promise for the treatment of AD in future. The formation of amyloids in neurons and the formation of amylin in pancreatic cells are potential links between these two disorders, which can be silent killers.

Comparative Studies of Salivary and Blood Sialic Acid, Lipid Peroxidation and Antioxidative Status in Oral Squamous Cell Carcinoma (OSCC).

Objective : Oral squamous cell carcinoma (OSCC) is considered to be a serious life threatening issue for almost two decades. The objective of this study was to evaluate the over production of lipid peroxidation (LPO) byproducts and disturbances in antioxidant defense system in the pathogenesis of oral cancer. Methods : Lipid peroxidation and antioxidant status in OSCC patients were estimated and compared the sensitivity and specificity of circulating biomarkers (MDA, Sialic acid, Catalase, SOD, GSH and Neuraminidase) with β-2 microglobulin (β-2MG) at different thresholds in blood and saliva using receiver operating characteristics (ROC) curve design. R esults : Our results showed that the levels of MDA and Sialic acid were significantly increased in plasma of OSCC patients as compared to healthy subjects whereas antioxidant level was significantly decreased. Conclusion : ROC analysis indicated that MDA in saliva is a better diagnostic tool as compared to MDA in blood and β-2MG in blood is better diagnostic marker as compared to β-2MG level in saliva.

Molecular Characterization of FLT3 Mutations in Acute Leukemia Patients

Fms-like tyrosine kinase 3 (FLT3) performs a vital role in the pathogenesis of hematopoietic malignancies. Therefore in recent times, the focus of several studies was on use of FLT3 as a prognostic marker. The present study investigated the molecular characterization and incidence of FLT3 mutations in acute leukemia patients in Pakistan. A total of 55 patients were studied, of which 25 were suffering from acute lymphoblastic leukemia (ALL) and 30 were suffering from acute myeloid leukemia (AML). The polymerase chain reaction demonstrated FLT3/ ITD mutations in 1 (4%) of 25 ALL patients, a male with the L2 subtype. In AML cases the rate was 4 (13.3%) of 30, three males and one female. The AML-M4 subtype was found in three and the AML M2 subtype in the other. In the AML cases, a statistically significant (p=0.009) relationship was found between WBC (109/L) and FLT3/ ITD positivity. However, no significant relationship was found with other clinical parameters (p>0.05). In acute myeloid leukemia (AML) FLT3/ITD+ mutation was more prevalent in elderly patients 31-40 age groups, 21-30 and 51-60 age groups respectively. In acute lymphoblastic leukemia (ALL) statistically no significant relationship was found between clinical features and FLT3/ITD positivity (p>0.05). However, in acute lymphoblastic leukemia (ALL) FLT3/ITD+ mutation was more commonly found in age groups of 21-30.