Synthesis and mycobactericidal properties of metal complexes of isonicotinoyldithiocarbazic acid

An isonicotinoyldithiocarbazic acid (IN-DtczH) ligand, synthesized from isoniazid, was complexed with transition metals and evaluated for anti-mycobacterial activity as well as toxicity towards human-transformed rhabdomyosarcoma (RD) cells in vitro. Complexes with Ni, Co and Zn showed MIC of 2, 2 and 50 μg/ml against Mycobacterium tuberculosis H₃₇Rv, and 10, 100 and 50 μg/ml against a multidrug-resistant strain of M. tuberculosis. They had little cytotoxic effect on the RD cells. In contrast, the Cu complex was highly cytotoxic with a low anti-mycobacterial activity.     

Functional characterization of the phospholipase C activity of Rv3487c and its localization on the cell wall of Mycobacterium tuberculosis

Mycobacterium tuberculosis survives and persists for prolonged periods within its host in an asymptomatic,latent state and can reactivate years later if the host's immune system weakens. The dormant bacilli synthesize and accumulate triacylglycerol, reputed to be an energy source during latency. Among the phospholipases, phospholipase C plays an important role in the pathogenesis. Mutations in a known phospholipase C, plcC, of M.tuberculosis attenuate its growth during the late phase of infection in mice. Hydrolysis of phospholipids by phospholipase C generates diacylglycerol, a well-known signalling molecule that participates in the activation of extracellular signal-regulated kinases (ERK) through protein kinase C leading to macrophage activation. In the present study, we show that M.tuberculosis possesses an additional cell wall-associated protein, Rv3487c, with phospholipase C activity. The recombinant Rv3487c hydrolyses the substrate phosphatidylcholine and generates diacylglycerol by removing the phosphocholine. Furthermore, Rv3487c is expressed during infection as it exhibits significant humoral immunoreactivity with sera from children with tuberculosis, but not with that from adult patients.     

Highly pathogenic simian immunodeficiency virus mne variants that emerge during the course of infection evolve enhanced infectivity and the ability to downregulate CD4 but not class I major histocompatibility complex antigens

The replicative, cytopathic, and antigenic properties of simian immunodeficiency virus (SIV) variants influence its replication efficiency in vivo. To further define the viral properties and determinants that may be important for high-level replication in vivo and progression to AIDS, we compared a minimally pathogenic SIVmne molecular clone with two highly pathogenic variants cloned from late stages of infection. Both variants had evolved greater infectivity than the parental clone due to mutations in nef. Interestingly, a pol determinant in one of the highly pathogenic variants also contributed to its increased infectivity. Furthermore, because replication in vivo may also be influenced by the ability of a virus to evade the cellular immune response of the host, we examined whether the variants were more capable of downregulating surface expression of class I major histocompatibility complex (MHC). Decreased MHC class I expression was not observed in cells infected with any of the viruses. Furthermore, the Nef proteins of the highly pathogenic variants only slightly reduced surface MHC class I expression in transfected cells, although they efficiently downregulated CD4. Together, these data demonstrate that mutations which can enhance viral infectivity, as well as CD4 downregulation, may be important for efficient replication of SIV in the host. However, Nef-mediated reduction of MHC class I expression does not appear to be critical for the increased in vivo replicative ability of highly pathogenic late variants.     

Early onset of the maximum protein anabolic effect induced by isoproterenol in chick skeletal and cardiac muscle

Prolonged (120 days) oral administration of a beta adrenoceptor agonist, isoproterenol hydrochloride (dose = 1.5 mg/kg body weight) resulted in an increase in the live weight of growing chicks (Callus domesticus). Measurement of dry muscle mass and total proteins in muscle homogenates from M. pectoralis major. M. petoralis minor suggested a muscle hypertrophy largely responsible for this live weight increase. Further, an increase in organ weight and total tissue proteins supported cardiac hypertrophy in chicks as a result of isoproterenol administration. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) revealed alterations in actin myosin profiles implying a drug induced change in phenotypic expression of myofibrillar component of both skeletal and cardiac muscle. The results suggest that prolonged treatment of chicks produced changes that were not much different from those recorded immediately within a fortnight.     

A new membrane probing steroidal spin label: synthesis and applications

The applicability of a new steroidal spin label, 3-oxo-androstan-17 beta-yl-(2",2",6",6"-tetramethyl-N-oxyl) piperidyl butan-1',4'-dioate, in studying the phase transition properties of model membrane L-alpha-dipalmitoyl phosphatidyl choline (DPPC) in the presence and absence of drugs has been explored. Its synthesis and characterization has been described herein. Besides, the localization of this spin label in lipid liposomes has been studied using electron spin resonance (ESR), differential scanning calorimetry (DSC) and 1H and 31P NMR spectroscopic techniques. The label has also been used to study the permeability of epinephrine into membrane. The results show that the spin label has a good potential as a spin probe in the study of biomembranes.     

Critical factors governing the efficient direct organogenesis in green-fleshed kiwifruit (Actinidia deliciosa) [A. Chev.] var. deliciosa

In Vitro Cellular & Developmental Biology - Plant - The present study was focused towards determining the factors governing direct organogenesis in kiwifruit cultivar ‘Allison’....     

The validity of self-reported weight change among adolescents and young adults

Objective: To assess the association of weight change based on serial self‐reported vs. measured weights. Research Methods and Procedures: Two thousand two hundred eighty‐four male and 2476 female participants in the National Longitudinal Study of Adolescent Health who provided information on weight at Waves II and III and were at least 16 years of age were studied. Linear regression was used to assess predictors of the discrepancy between weight change based on self‐reported vs. measured weights. Logistic regression was used to identify predictors of self‐report correctly classifying participants in terms of weight change category. Results: Self‐reported weight was slightly lower than measured weight at Waves II and III, but weight change based on self‐reported weights underestimated true weight change by only 2.1 (female participants) to 2.8 (male participants) pounds. Overweight and obese female participants were consistent in their under‐reporting of their weight more than their leaner peers; thus, the discrepancy between weight change from Wave II to Wave III based on serial self‐reports vs. measured weights was significantly smaller among the obese female vs. healthy‐weight female participants (0.3‐ vs. 2.3‐pound underestimation, p < 0.05). Among the male participants, the same pattern was evident. African‐American ethnicity, Hispanic ethnicity, the level of physical activity, the hours per week watching television, and weight change efforts were not related to the discrepancy between weight change based on self‐reported vs. measured weights. Discussion: The discrepancy between weight change based on self‐report vs. measured weights was minor and not related to race, weight change efforts, activity, or inactivity, thus suggesting that much of the error is random.     

Race and gender differences in the association of dieting and gains in BMI among young adults

Objective: To assess the relationship between dieting and subsequent weight change and whether the association varies by gender or race/ethnicity. Research Methods and Procedures: Male (n = 4100) and female (n = 4302) participants in the National Longitudinal Study of Adolescent Health who provided information on weight and height at baseline and two follow‐up assessments and were not missing information on weight control strategies or race were studied. Generalized estimating equations were used to assess whether dieting to lose or maintain weight at Wave I or II predicted BMI (kg/m²) change between adolescence and young adulthood (Wave II to III). Analyses were stratified by gender and took sampling weights and clustering into account. Results: At Wave I, the mean age of the participants was 14.9 years. Approximately 29.3% of female participants and 9.8% of male participants reported dieting in Wave I or II. Fewer African Americans than whites (6.2% vs. 10.0% and 25.5% vs. 31.2%, p = 0.007 and p = 0.02, among males and females, respectively) reported dieting. Between Waves II and III, participants gained on average 3.3 kg/m². Independent of BMI gain during adolescence (Waves I to II), female participants who dieted to lose or maintain weight during adolescence made larger gains in BMI during the 5 years between Waves II and III (mean additional gain, 0.39 kg/m²; 95% confidence interval, 0.08 to 0.71) than their nondieting peers. The association was not significant among the male participants. The association was largest among African‐American female participants. Discussion: The results suggest that not only is dieting to lose weight ineffective, it is actually associated with greater weight gain, particularly among female adolescents. Female African‐American dieters made the largest BMI gains.