Pharmacoeconomic analysis of treatment of patients infected with hepatitis C virus.

Hepatitis C infection imposes a high economic burden globally. It has been estimated that in 2012, the healthcare cost of Hepatitis C virus (HCV) was $6.5 billion. Furthermore, it has been projected that the cost will reach at $9.1 billion by the year 2024.Frequency of hepatitis C in Pakistan is significantly higher (4.5%) when compared to the populations like India (0.7%), Nepal (1.0), Myanmar (2.5%), Iran (0.8%), China (1%) and Afghanistan (1.1%). The current standard of care for chronic infection with hepatitis C virus is 24 or 48 weeks of therapy with Pegylated interferon-alfa-2a (Peg INF) +Ribavirin (RV) or Interferon alfa-2a (INF) + RV. The objective of this study was to determine that which combination is more effective and the gain in sustained virologic response (SVR) is worth the incremental cost. In total 84 patients were enrolled who received current standard treatment of care for chronic infection with HCV either 24 or 48 weeks of therapy with Peg INF + RV or INF + RV. A pharmacoeconomic analysis was done including fixed and variable cost (comprising concomitant therapies, emergency visits and hospital admissions) of both treatment regimens were calculated and compared with the SVR accomplished by the patients. It was concluded that the Peg INF + RV is cost effective as compared with conventional INF + RV for the treatment of adult patients infected with HCV genotype 3a under a varied array of possibilities regarding treatment costs and effectiveness.

Improvement in Therapeutic Ability of Wharton's Jelly Derived Mesenchymal Stem Cells with Vitamin E in Breast Cancer.

OBJECTIVE: To assess the role of Vitamin E to improve the survival of Wharton's jelly derived mesenchymal stem cells (WJMSCs) in breast cancer conditions. STUDY DESIGN: An experimental study. PLACE AND DURATION OF STUDY: Centre for Research in Molecular Medicine, University of Lahore, from November 2016 to March 2017. METHODOLOGY: WJMSCs were obtained from umbilical cord tissue with enzyme digestion method. Isolated cells were characterized for CD90 and CD45 by immunocytochemistry. Pretreatment and conjugation therapies of vitamin E in 50mM and 100mM concentration were used on WJMSCs and breast cancer plasma was provided to mimic the cancer conditions, while WJMSCs provided with normal plasma were considered control. Cells' viability, proliferation and death were evaluated by crystal violet staining, MTT assay and LDH assay, respectively. Oxidative stress was observed by activity of anti-oxidant enzymes (GSH, catalase, SOD) and reactive oxygen species (MDA). RESULTS: The isolated cells expressed mesenchymal stem cells marker CD90 and lacked hematopoietic marker CD45. Vitamin E improved the viability and proliferation of WJMSCs in normal plasma, in conjugation with breast cancer plasma and in pretreatment groups but conjugation group showed even better results with concentration of 100mM as compared to the pretreatment group and opposite was observed for LDH assay for cells death analysis. Vitamin E also reduced the oxidative stress in 100mM more pronounced in conjugation group as compared to pretreatment group while left no harmful effects on WJMSCs in normal plasma. CONCLUSION: Vitamin E conjugation with breast cancer conditions significantly improved growth of WJMSCs. Thus vitamin E treated WJMSCs are better therapeutic options for breast cancer.

Effect of Nicotinic Acid (Vitamin B3 or Niacin) on the lipid profile of diabetic and non - diabetic rats.

OBJECTIVE: To determine the efficacy of nicotinic acid on the lipid profile of diabetic and non diabetic rats. METHODS: This was an experimental study done at the Institute of Molecular Biology and Biotechnology, The University of Lahore, Pakistan between May 2010 to July 2010. Nicotinic acid was administered to a hypercholesterolemic group and a hypercholesterolemic + diabetic Group of Albino rats for 42 days and response to therapy was recorded on day 21 and day 42 of the experiment. Comparison among these two groups as well as three control groups was determined by Analysis of Variance (ANOVA) and differences were considered significant at (P<0.05). A total of 50 rats were included in the study. RESULTS: Lipid profile of the hypercholesterolemic group as well as hypercholesterolemic + diabetic group as compared with the control groups showed highly significant improvement on the day 21 and day 42 of the experiment. The values of serum total cholesterol (TC), triglycerides (TG), low density lipoprotein (LDL) cholesterol and total lipids (TL) showed highly significant decrease whereas serum high density lipoprotein (HDL) cholesterol showed highly significant increase. CONCLUSION: Nicotinic acid is the most effective agent available in increasing HDL cholesterol and lowering serum TC, triglycerides (TG), LDL cholesterol and TL in hypercholesterolemic Diabetic and hypercholesterolemic non-diabetic Albino rats.

Hypotensive effect of chemical constituents from Aloe barbadensis.

Hypotensive effects of aloeemodin, aloin A, elgonica dimer A and bisbenzopyran from Aloe barbadensis have been studied. Aloeemodin has emerged as a potent hypotensive agent in current pharmacological investigations and caused 26 %, 52 %, and 79 % falls in mean arterial blood pressure at the corresponding doses of 0.5, 1, and 3 mg/kg in rats. The paper also describes the absolute configuration of elgonica dimer A (1).

Hypotensive, hypoglycaemic and toxicological studies on the flavonol C-glycoside shamimin from Bombax ceiba.

Shamimin, a C-flavonol glucoside from Bombax ceiba leaves showed significant potency as a hypotensive agent at the doses of 15 mg/kg, 3 mg/kg, 1 mg/kg and significant hypoglycaemic activity at 500 mg/kg in Sprague-Dawley rats. Further studies revealed that it did not cause any mortality in mice at the dose of 1 g/kg but in rats 500 mg/kg is a lethal dose. Aqueous and methanolic extracts of Bombax ceiba leaves and one of its fractions were also subjected to pharmacological and toxicological screening.

Carbohydrate moiety of Plasmodium falciparum glycoproteins: the nature of the carbohydrate-peptide linkage in the MSP-2 glycoprotein.

Metabolic labelling of Plasmodium falciparum parasites with [3H]GlcN, [3H]Man, [3H]Gal and [3H]ethanolamine, and subsequent purification by SDS-PAGE of the labelled material provided effective labelling of the MSP-1, 195 kDa, and MSP-2, 42-53 kDa, glycoproteins. Reductive beta-elimination of the MSP-2 released from the gel consisted of glycopeptides containing labelled sugars. Processing of the eliminated components and identification of the sugar residues demonstrated the presence of N-acetylglucosaminitol and N-acetylgalactosaminitol amongst other labelled sugars. Reductive beta-elimination with sodium hydroxide-sodium borotritide-borohydride showed the presence of glucosaminitol and alanine in the hydrolysis products. The MSP-2 was retained on solid phase wheat-germ agglutinin and was released from the lectin by treatment with GlcNAc. Upon treatment with O-glycanase the MSP-2 glycoprotein released labelled amino sugar, and derived oligosaccharides on treatment with exoglycosidases released labelled components corresponding to the metabolically incorporated sugars. Labelled Gal was incorporated into the MSP-2 glycoprotein using [3H]UDP-Gal and galactosyltransferase. The galactosylated glycoprotein released labelled Gal upon treatment with beta-galactosidase. The results of the present study suggest that the carbohydrate chains of the MSP-2 glycoprotein are attached to the protein backbone via GlcNAc- and GalNAc-serine/threonine in O-glycosyl linkage and the glycoprotein has terminal GlcNAc and Gal residues. The carbohydrate moieties of MSP-2, glycoprotein consist mainly of short chains linked to the protein core.

A new bisbenzopyran from Aloe barbadensis roots.

A new bisbenzopyran (1) has been isolated from the methanolic extract of roots of Aloe barbadensis through solvent separation and vacuum liquid chromatography. Based on spectral analysis including 2D-NMR (COSY, NOESY, J-resolved, HMQC, and HMBC) techniques, the structure of compound 1 was assigned as 3,3'-bis(3,4-dihydro-4-hydroxy-6-methoxy-2 H-1-benzopyran).

Effect of chemotherapy on circulating steroid hormone levels in postoperative premenopausal breast cancer patients.

Serum levels of 17-beta oestradiol, testosterone and progesterone were determined in postoperative premenopausal breast cancer patients. In patients receiving chemotherapy circulating 17-beta oestradiol values decreased significantly compared to control group during the sampling/drug regimens employed. Among the control group, however, the oestradiol levels remained high throughout the sampling period. Testosterone levels in patients were also significantly low compared to control group throughout the sampling regimen up to 28 days. In contrast the levels of progesterone in patients were elevated and remained high compared to the corresponding controls. A positive correlation was found between the drop in serum oestradiol and testosterone levels following the initiation of chemotherapy and the regression of the tumour size. Steroid hormone levels in the serum of breast cancer patients receiving chemotherapy can serve as clinical tools to monitor the progress of the disease and response to therapy.

Bacillus sphaericus as mosquito larvicide.

In Noorpur Shahan, a village in the outskirts of Islamabad, Bacillus sphaericus was tested to determine its efficacy against mosquito larvae. Since the creation of this new Islamabad district no mosquito control measure has been taken in the area and like so many other places in and around Islamabad, mosquito density is unusually high in this village. The efficacy of Bacillus sphaericus was studied upto seven weeks after its application and it gave good larval control.

Effect of anticalmodulin drugs on testosterone synthesis in hCG stimulated mouse Leydig cells.

The effect of three anticalmodulin drugs, prepared in this laboratory and a commercially available drug Mastoparan, was tested on the secretion (or synthesis) of testosterone in hCG stimulated Leydig cells. The results of the use of drugs RN-IV A, RN-IV B and RN-IV C indicated that hCG (10 ng/ml), DbcAMP (0.1 mM) and cholera toxin (2 micrograms/ml)-stimulated testosterone production was inhibited in Leydig cells in a dose dependent manner. In hCG stimulated cells, the ID50 for drug RN-IV A was 2 microM, for drug RN-IV B was 25 microM and for drug RN-IV C was 130 microM. Based on ID50 the most effective drug was RN-IV A. Maximum inhibition of testosterone production was obtained at a concentration of 20 microM for drug RN-IV A, 150 microM for drug RN-IV B and 200 microM for drug RN-IV C. Further extensive experiments with drug RN-IV B showed that (a) at 100 microM concentration the drug does not impair the binding of receptor with 125I hCG, (b) the cAMP accumulation was prevented in a dose dependent manner reaching a minimal of 1.1 pM at 50 microM, compared with 3.5 pM in hCG (10 ng/ml) stimulated cells. The drug RN-IV B at a concentration of 100 microM, which failed to prevent conversion of exogenous pregnenolone or progesterone to testosterone, otherwise caused complete inhibition of testosterone production in hCG stimulated cells. Mastoparan also inhibited testosterone production in hCG stimulated cells in a dose dependent manner.(ABSTRACT TRUNCATED AT 250 WORDS)

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 testosterone on epididymal proteins in castrated rhesus monkeys.

The effect of testosterone on regulation of epididymal protein synthesis has been investigated in castrated rhesus monkeys (Macaca mulatta). The proteins in the treated monkeys were characterized using polyacrylamide gel electrophoresis (under nondenaturing and denaturing conditions) and electrofocusing. At least four distinct proteins have been shown to be synthesized by the monkey epididymis under testosterone influence. Two of these proteins were detected following two days of testosterone treatment while the other two proteins were detected after a six-day treatment period. None of these proteins was detectable in monkeys treated with estradiol for six days. Electrofocusing of epididymal cytosol proteins from untreated and testosterone-treated and castrated monkeys also confirmed the presence of four androgen-dependent proteins in this species. The isoelectric points of these proteins were shown to range between 5.8 and 6.4. The molecular weights of these proteins were found to vary between 47,500 and 66,000. The in vitro incorporation of 3H-labeled amino acids was markedly greater in the androgen-primed epididymis as compared with the control tissue.

Effect of an LHRH analogue on testicular function in the immature monkey (Macaca mulatta).

Response of the immature monkey testis to an LHRH analogue, D-Ser-(TBu)6-EA10-LHRH, has been assessed by measuring testicular androgen production in the immature rhesus monkey. Administration of the analogue (2.5 micrograms X 2 daily) for 5 days induced a significant increase in testicular testosterone compared with untreated animals. The response of the control and the LHRH-agonist treated monkey testis to gonadotrophin (hCG) was assessed by in vitro androgen production. Whereas the testicular tissue from LHRH analogue primed monkeys responded to in vitro stimulation of hCG, no significant increase in androgen production was observed when testicular tissue from untreated animals was incubated with the gonadotrophin. The present data suggest a functional differentiation of the immature monkey testis following the LHRH analogue treatment.

In vitro influence of some mammalian pituitary and placental hormones on androgen production by the lizard testis.

Effect of mammalian pituitary and placental hormones has been studied on in vitro androgen production by the testis of the spiny-tailed lizard, Uromastix hardwicki. Aliquots of pooled testicular tissue from adult lizards were incubated individually with 1 microgram each, of oFSH, oLH, oTSH and 1 IU each of hCG, PMSG, and ACTH. Androgen was measured by testosterone radioimmunoassay in both the tissue and the incubation medium. Severalfold increase in androgen production was observed in the testicular tissue incubated with FSH, LH, TSH nd PMSG. Maximum stimulation was obtained with FSH. hCG also caused a measurable increase in androgen production but was much less potent than PMSG. Incubation of testicular tissue with ACTH did not result in a significant change in androgen production as compared to the controls. The hormonal specificity for steroidogenesis by the lizard testis has been discussed in the light of these results.

Effects of gonadotrophin treatment in vivo on testicular function in immature rhesus monkeys (Macaca mulatta).

Changes in testicular histology and concentrations of testosterone and oestradiol 17 beta in testicular tissue and plasma have been studied following administration of gonadotrophins (oFSH, oLH, hCG and PMSG) to immature male monkeys. Treatment with FSH (1 mg/day) or PMSG (100 IU/day) for five days, induced a marked enlargement of the seminiferous tubules and increase in the Sertoli cell cytoplasm. Injections of LH (1 mg/daily) or hCG (100 IU/daily) administered similarly, failed to produce hypertrophy of the Sertoli cell. In LH, hCG and PMSG stimulated testes morphologically differentiated interstitial cells could be recognized. FSH did not produce any detectable effect on the intertubular tissue. A significant increase in testicular and plasma testosterone levels was observed with LH, hCG and PMSG. FSH was shown to be much less effective in stimulating androgenesis. An increase in testicular oestradiol production over that of controls, was observed in FSH and PMSG treated monkeys but not in animals treated with LH or hCG.