Cadmium exposure in tobacco workers: possible renal effects.

Cadmium is a nephrotoxic metal widely used in industry and the main source of Cd in general population is smoking. Considering that the source of Cd in cigarettes is the tobacco leaf, the exposure to Cd was evaluated in workers employed at a tobacco leaf processing factory. Blood and urinary Cd levels were measured by flameless atomic absorption spectrometry in 87 workers and 35 controls. Urinary enzymes, total protein, albumin and uric acid were also determined to investigate the possible nephrotoxic effects of Cd. Blood Cd levels were significantly higher in workers (1.63 +/- 1.95 microg/L) than in controls (0.91 +/- 1.15 microg/L) (p = 0.044). The increase observed in urinary Cd levels of workers was non significant (0.56 +/- 0.5 microg/g creatinine in workers and 0.46 +/- 0.5 microg/g creatinine in controls). Both in workers and in controls, subjects smoking >10 cigarettes/day showed significantly increased blood Cd levels compared to non-smokers (p = 0.000 and p = 0.011, respectively). In workers, urinary alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), total protein, and uric acid were observed to be significantly increased (p = 0.013, p = 0.000, p = 0.000, p = 0.025, respectively), ALP, GGT and total protein being positively correlated with Cd in urine. In conclusion, the workers in the tobacco leaf processing factory were found to be exposed to Cd compared to the general population. The increase in the urinary enzymes and proteins suggests that an exposure to Cd affects kidney functions even below the toxic limits generally accepted.     

Immunochemical characterisation of megakaryocyte potentiator activity from mouse bone marrow

Megakaryocyte potentiator derived from mouse bone marrow has been shown to be immunologically similar to Interleukin-6 (IL-6). In this study the activity has been characterised by biochemical and immunochemical techniques. The activity is described as a O-linked glycosylated molecule with an apparent MW of 15 Kd and pl of the range pH 5.9–6.35. The data show that mouse bone marrow potentiator activity is a variant of IL-6 and with the potential to enhance megakaryocyte growth. © 1995 Wiley-Liss, Inc.     

Synthesis,Cancer‐Selective Antiproliferative and Apoptotic Effects of Some (±)‐Naringenin Cycloaminoethyl Derivatives

Naringenin is a naturally occurring flavonoid and due to its broad spectrum of biological activities, including anticancer properties, has attracted scientific attention in recent years. To contribute to these studies, we synthesized some new (±)‐naringenin cyclic aminoethyl derivatives, analyzed the cytotoxic and anti‐proliferative properties of them via 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl‐2H‐tetrazolium bromide (MTT) assay, and mitochondrial apoptosis signaling response and gene expressions belong to caspase‐3 depended apoptosis as biomarkers in both healthy and cancer cell lines. Our results suggest that some of our naringenin derivatives are potential anticancer agents with a selective death potential and targeting properties for mitochondrial apoptosis signaling against at least human cervix and breast cancer.     

A novel templates of piperazinyl-1,2-dihydroquinoline-3-carboxylates: Synthesis,anti-microbial evaluation and molecular docking studies

A series of piperazinyl-1,2-dihydroquinoline carboxylates were synthesized by the reaction of ethyl 4-chloro-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxylates with various piperazines and their structures were confirmed by ¹H NMR, ¹³C NMR, IR and mass spectral analysis. All the synthesized compounds were screened for their in vitro antimicrobial activities. Further, the in silico molecular docking studies of the active compounds was performed to explore the binding interactions between piperazinyl-1,2-dihydroquinoline carboxylate derivatives and the active site of the Staphylococcus aureus (CrtM) dehydrosqualene synthase (PDB ID: 2ZCQ). The docking studies revealed that the synthesized derivatives showed high binding energies and strong H-bond interactions with the dehydrosqualene synthase validating the observed antimicrobial activity data. Based on antimicrobial activity and docking studies, the compounds 9b and 10c were identified as promising antimicrobial lead molecules. This study might provide insights to identify new drug candidates that target the S. aureus virulence factor, dehydrosqualene synthase.     

Intermediary carbohydrate metabolism in the adult filarial worm Setaria digitata.

Several key enzymes related to carbohydrate metabolism were assayed in Setaria digitata. In the cytosolic fraction pyruvate kinase, phosphoenolpyruvate carboxykinase, malate dehydrogenase, malic enzyme, aspartate transaminase and alanine transaminase were found. Among the TCA cycle enzymes succinate dehydrogenase, fumarate reductase, fumarase (malate dehydration), malate dehydrogenase (malate oxidation and oxaloacetate reduction) and malic enzyme (malate decarboxylation) were detected in the mitochondrial fraction. Only reduced nicotinamide adenine dinucleotide (NADH) dehydrogenase, NADH oxidase and NADH-cytochrome c reductase were found in the mitochondrial fraction. The significance of these results with respect to the metabolic capabilities of the worm are discussed.     

Effects of estrous cycle stage and transport temperature of ovaries on in vitro maturation of canine oocytes

Unlike other domestic animals, in vitro maturation (IVM) of canine oocytes still has limited success. The present study investigated the effects of estrous cycle stage and transport temperature of ovaries on in vitro maturation of canine oocytes. The donor bitches were categorized into three groups based on stage of estrus cycle: follicular (proestrus or estrous), luteal (diestrus) and anestrus. One ovary of each pair collected from 39 mature bitches was transported in Phosphate Buffer Saline (PBS) at 4 °C while the other was transported at 37 °C. A total of 1138 Grade I COCs obtained from all ovaries were grouped and matured in modified synthetic oviduct fluid (mSOF) supplemented with follicle stimulating hormone (FSH), luteinizing hormone (LH), essential and non-essential amino acids at 38.5 °C in a humidified 5% CO₂, 5% O₂, and 90% N₂ atmosphere for 72 h. The nuclear maturation rates were evaluated by aceto–orcein staining.Oocytes harvested from follicular and luteal ovaries have a significantly higher maturation rates (MI + MII) than the oocytes from anestrual ovaries in the 37 °C group (p < 0.05). However, oocytes harvested from anestrual ovaries transported at 4 °C had the highest maturation (MI + MII) rate, and the difference between anestrual and luteal ovary groups was significant (p < 0.05). The oocytes from anestrual ovaries transported at 4 °C have significantly higher maturation rates than those transported at 37 °C (p < 0.0001). However, the transport temperature (37 or 4 °C) did not significantly affect the maturation (MI + MII) rates of oocytes harvested from the luteal (p = 0.61) and follicular (p = 0.48) stage ovaries.It can be concluded from this study that (1) both transport temperature and transport temperature × estrus cycle stage interaction effected the maturation rates, while estrus cycle stage alone did not, and (2) transporting canine ovaries at 4 °C can improve in vitro maturation rates in oocytes harvested from anestrous ovaries.     

A Comparison of Mouse Parvovirus 1 Infection in BALB/c and C57BL/6 Mice: Susceptibility,Replication, Shedding,and Seroconversion

This study characterized the effects of challenge with a field isolate of mouse parvovirus 1 (MPV1e) in C57BL/6NCrl (B6) and BALB/cAnNCrl (C) mice. We found that C mice were more susceptible to MPV1e infection than were B6 mice; ID₅₀ were 50 to 100 times higher after gavage and 10-fold higher after intraperitoneal injection in B6 as compared with C mice. To evaluate the host strain effect on the pathogenesis of MPV1e, B6 and C mice were inoculated by gavage. Feces and tissues, including mesenteric lymph nodes (MLN), ileum, spleen and blood, were collected for analysis by quantitative PCR (qPCR) to assess infection and fecal shedding and by RT-qPCR to evaluate replication. Peak levels of MPV1e shedding, infection, and replication were on average 3.4, 4.3, and 6.2 times higher, respectively, in C than in B6 mice. Peaks occurred between 3 and 10 d after inoculation in C mice but between 5 and 14 d in B6 mice. Multiplexed fluorometric immunoassays detected seroconversion in 2 of 3 C mice at 7 d after inoculation and in all 3 B6 mice at 10 d. By 56 d after inoculation, viral replication was no longer detectable, and fecal shedding was very low; infection persisted in ileum, spleen, and MLN, with levels higher in C than B6 mice and highest in MLN. Therefore, the lower susceptibility of B6 mice, as compared with C mice, to MPV1e infection was associated with lower levels of infection, replication, and shedding and delayed seroconversion.Abbreviations: B6, C57BL/6; C, BALB/c; MFI, median fluorescence intensity; MFIA, multiplexed fluorometric immunoassay; MLN, mesenteric lymph node; MMV, mouse minute virus; MPV, mouse parvovirus; NS1, nonstructural protein 1; qPCR, quantitative PCR; r, recombinant; Rn, normalized reporter value; VP2, virus capsid protein 2Parvoviruses are small (20 to 28 nm), nonenveloped icosahedral single-stranded DNA viruses that infect a diverse range of vertebrate and arthropod species. Much of what is understood about the biology and pathogenesis of autonomous parvoviruses has been derived from studies of the original murine parvoviral isolates, particularly the prototypic and immunosuppressive strains of mouse minute virus (MMV).^9,13,32 Because autonomous parvoviruses have a requirement and predilection for proliferating cells to replicate, they are primarily teratogenic pathogens. In contrast, rodent parvovirus infections of older animals are usually asymptomatic, because the cells that divide in mature animals, such as enterocytes, lymphoreticular cells, and hematopoietic cells, are largely spared.^2,47,48 The most common parvovirus of laboratory mice, mouse parvovirus 1 (MPV1), was first isolated²⁹ from mouse T-lymphocyte cultures that had lost viability or the ability to proliferate when stimulated. In contrast to MMV,^10,27,40 MPV1 has not been shown to cause disease in newborn or immunodeficient mice^19,45 but nevertheless has been reported to modulate the immune response of infected mice.^30,31Adventitious infections of laboratory mice with MPV1 and other parvoviruses continue to occur regularly, despite biosecurity improvements that have successfully excluded once-common pathogens such as Sendai virus.^22,37,39 One reason for the continued occurrence of these infections is that nonenveloped parvovirus virions are environmentally stable and resistant to disinfection.^18,49 Furthermore, related to their tendency to persist in host tissues even after seroconversion and their predilection for dividing cells, parvoviruses have been among the most frequent viral contaminants of transplantable tumor lines and other rodent-derived biologic reagents.^34,35 Inoculation of parvovirus-contaminated biologic reagents into experimental animals can contribute to the incidence of parvoviral outbreaks. Currently, mouse populations typically are housed in microisolation cages and are monitored for MPV1 infections through the use of soiled bedding sentinels. An MPV1 infection of the principal animals may not be transmitted to sentinels when the prevalence of infection is low, as is often the case after contamination, or when the sentinels are comparatively resistant to infection because of their genetic background or age.^7,16,17 However, a recent study found that sentinel age did not affect the likelihood of MPV1 infection.¹⁷The C57BL/6 (B6) mouse strain is popular in biomedical research and is commonly used as the background strain for spontaneous and genetically engineered mutations. We and others have noted that B6 mice are less likely to be MPV1 seropositive than are mice of other strains and stocks, even in facilities where MPV1 is widespread.⁴⁴ There has been speculation that B6 mice might not seroconvert when infected with MPV1. However, data reported here and by others^7,15 indicate that B6 mice are less likely to seroconvert because they are comparatively resistant to MPV1 infection; when they become infected, they do seroconvert. The current study evaluated whether resistance of B6 mice to infection with MPV1, as compared with BALB/c (C) mice, varies with virus inoculation route and correlates with differences in the time course and levels of viral infection, replication, and shedding and of humoral immunity.Most studies of MPV1 in mice have been performed with the cultivable MPV1a strain.^{7,19,30,31,45} Cultivable murine parvoviruses are known to differ from wildtype strains genetically and in their cell tropisms, pathogenicity, and transmissibility in vivo. For example, MPV1d, a noncultivable field isolate, was more readily transmitted to sentinels than was MPV1a.¹¹ We therefore chose to perform the current experiments with MPV1e,^3,4 a representative field strain that we originally isolated from an adventitiously infected barrier colony⁴⁴ and that has been propagated only in mice.