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Biomedical subjects

M Martinez

Publications and source records attributed to M Martinez.

At least 37 records · Page 2Linked to original sources

Ultrastructure of the urethra of the Mongolian gerbil.

OBJECTIVE: The urethra is the main port of entry of sexually transmitted pathogens. However, papers on the morphology of the urethra are scarce. The Mongolian gerbil is a rodent native of the Mongolia and China and has been utilized as a laboratory animal since the 1960s. This work describes the ultrastructure of the urethra of the Mongolian gerbil to provide data for future experimental studies. METHODS: The urethra of ten adult male gerbils was studied by transmission electron microscopy. RESULTS: The epithelium of the pelvic urethra possesses two cell types: I and II, without the formation of cellular layers, while the penile urethra possesses cellular layers: basal, intermediate and superficial. The urethra presents neurosecretory cells belonging to the amine precursor uptake and decarboxylation system. CONCLUSIONS: The urethral epithelium of the gerbil is a neurosecretory epithelium, part of the amine precursor uptake and decarboxylation system.

Animals↗

Direct measurements of urban OH reactivity during Nashville SOS in summer 1999.

Emissions of volatile chemicals control the hydroxyl radical (OH), the atmosphere's main cleansing agent, and thus the production of secondary pollutants. Accounting for all of these chemicals can be difficult, especially in environments with mixed urban and forest emissions. The first direct measurements of the atmospheric OH reactivity, the inverse of the OH lifetime, were made as part of the Southern Oxidant Study (SOS) at Cornelia Fort Airpark in Nashville, TN in summer 1999. Measured OH reactivity was typically 11 s(-1). Measured OH reactivity was 1.4 times larger than OH reactivity calculated from the sum of the products of measured chemical concentrations and their OH reaction rate coefficients. This difference is statistically significant at the 1sigma uncertainty level of both the measurements and the calculations but not the 2sigma uncertainty level. Measured OH reactivity was 1.3 times larger than the OH reactivity from a model that uses measured ambient concentrations of volatile organic compounds (VOCs), NO, NO2, SO2, and CO. However, it was within approximately 10% of the OH reactivity from a model that includes hydrocarbon measurements made in a Nashville tunnel and scaled to the ambient CO at Cornelia Fort Airpark. These comparisons indicate that 30% of the OH reactivity in Nashville may come from short-lived highly reactive VOCs that are not usually measured in field intensive studies or by US EPA's Photochemical Assessment Monitoring Stations.

Air Pollutants↗

Structure of the pelvic and penile urethra--relationship with the ducts of the sex accessory glands of the Mongolian gerbil (Meriones unguiculatus).

The urethra is the main place of entry for sexually transmitted pathogens. However, there is little literature on the morphology of the urogenital system, principally the urethra and ducts of the sex accessory glands. The Mongolian gerbil is an insectivorous, herbivorous and monogamous rodent with nocturnal habits; it has been used successfully as a laboratory animal since the 1960s. Therefore, the objective of the present paper was to describe the structure and ultrastructure of the urethra and its relations to the ducts of the accessory sex glands of the Mongolian gerbil (Meriones unguiculatus), contributing to the understanding of the reproductive biology of the rodent and aiming to provide data for future experimental studies. Conventional techniques of light and scanning electron microscopy were utilized. The urethra and ducts of the accessory sex glands are similar to those of the albino rat and the mouse. However, there is variation in drainage type among accessory sex glands for the inner urethra. The ducts of the seminal vesicle, the ductus deferens, drain their contents independently into the ampullary duct that opens in the urethra. The ducts of the prostate, coagulating and bulbourethral glands drain their contents independently into the urethra.

Animals↗

Genetic susceptibility to vaginal candidiasis.

To enable future studies on host resistance factors and therapy, inbred and outbred mouse strains were tested for susceptibility to vaginal candidiasis. Groups of mice were given 0.5 mg estradiol 3 days before and 4 days after intravaginal challenge with a suspension of Candida albicans. On day 1 after challenge, a swab was used to quantitate infection in all groups and to assure equivalent infection levels. On day 6, this was repeated and the experiment was terminated. BALB/c, the reference strain in repeated experiments, was susceptible, showing persistent infection with levels of cfu at day 6 falling within a range between a twofold decrease and a fourfold increase in relation to day 1 levels. CD-1 outbred mice were markedly resistant, with day 6 cfu levels showing a 74- to 87-fold decrease with respect to day 1 levels, whereas other outbred strains (CF-1, SW, ICR) were susceptible. A BALB/c substrain (ByJ) was also susceptible. With exception of CBA/J, which showed modest resistance, all inbred strains were similarly susceptible, including DBA/2, AKR/J, C3H/HeN, A/J and C57BL/6. The differences between CD-1 and BALB/c mice were also seen with a second C. albicans isolate. Our results show susceptibility to vaginal candidiasis is independent of the major histocompatibility locus H2 haplotype and any effect ascribable to use of particular commercial mouse suppliers. Differences among mouse strains in susceptibility to C. albicans, as seen in previous studies involving nonvaginal challenge routes, are not reflected in this vaginal candidiasis model; in general, such resistance patterns appear specific to the route of challenge administration. The resistance seen in mouse strain CD-1 is of particular interest in that CD-1 is known to be resistant to endocrine disruption by estrogen. Our results suggest this estrogen insensitivity may have broad-ranging effects on processes other than gametogenesis, including vaginal susceptibility to candidiasis.

Animals↗

Ultrastructural and morphometric analysis on the ovary of Wistar rats after chronic ethanol ingestion.

In the present study, seventy-two adult rats (Rattus norvegicus albinus) aged three months were used. The animals were divided into two groups (control and alcoholic). The control group received a solid diet (Purina rat chow) and tap water ad libitum. The alcoholic group received the same solid diet and sugar-cane liquid (trade 51, 41% Gay Lussac--GL) diluted 30% GL. At the end of 90, 180 and 270 days of treatment, ten rats of each group were anaesthetized with ethyl ether and sacrificed. The ovaries were collected, fixed, included and submitted to analysis by both light and electron microscopy. The alcoholic group showed increase in the number of corpora lutea at both 180 and 270 days of treatment, atresic follicles at 270 days of treatment, decreased diameter of corpora lutea at 180 and 270 days of treatment, the granulosa layer of the antral follicles at 180 days of treatment, and gradual regression of the theca antral follicles. Furthermore, an increase in diameter and posterior regression of the antral follicle were observed, as well as vacuolation, increased lipid droplets in the granulosa cell at 90 days and in the theca at 180 and 270 days of treatment and gradually in the interstitial cell. The rats showed ovarian alterations after ingestion of alcohol. There was a correlation between exposure time to the drug and the injury observed.

Alcohol-Induced Disorders↗

Overexpression of genes involved in vesicular trafficking to the vacuole defends against lethal effects of oxidative damage.

Anticancer bleomycins and structurally-related analogs are oxidative agents that mimic ionizing radiation in many of their cellular effects. The current study was designed to better understand this class of radiomimetic and oxidative drugs, and how cells defend against them to become resistant. Based on some of the properties conferred by the blm5-1 mutation of Saccharomyces cerevisiae, a multi-step cloning strategy was developed to search for genes that protect cells against oxidative damage and lethal effects of bleomycin treatments. The strategy employed blm5-1 mutant strains to search for genes that rescued the drug hypersensitivities conferred by the mutation, and utilized the inability of homozygous blm5-1 mutant diploid strains to grow at elevated temperatures. This approach identified the VPS3, VPS8 and PEP7 genes that function in vesicular trafficking between the endosome and the yeast vacuole via the carboxypeptidase Y (CpY) pathway. Mutant blm5-1 strains possess several phenotypic characteristics consistent with CpY mutants, including reduced mitotic growth rates and sporulative abilities. However, blm5-1 strains were not found to be defective in the transport of CpY into the vacuole. We suggest that the ability of the VPS3, VPS8 and PEP7 genes to rescue lethal effects of oxidative damage resulted from the overexpression of these genes.

Adaptor Proteins, Signal Transducing↗

Pleiotrophic cellular deficiencies conferred by the blm5-1 mutation of Saccharomyces cerevisiae.

Mutational alteration of the BLM5 gene of the model eukaryote, Saccharomyces cerevisiae, confers extreme hypersensitivities to lethal effects of ionizing radiation, anticancer bleomycins and structurally-related phleomycins. Additional properties conferred by the blm5-1 mutation in haploid and diploid strains were investigated for the current report. Only one copy of blm5-1 together with the normal BLM5 allele was sufficient to produce mitotic and meiotic defects in diploids, and greatly increase killing by bleomycin beyond wild type levels. Mitotic growth rates of blm5-1/blm5-1 homozygous mutant strains were slower than wild type or BLM5/blm5-1 heterozygous strains at 30 degrees C, and growth was nearly completely inhibited at 37 degrees C. Meiosis was inhibited at 30 degrees C and 37 degrees C in mutant homozygotes, and at 37 degrees C in BLM5/blm5-1 heterozygotes, while meiosis occurred at equivalent frequencies in wild type strains at both temperatures. Surprisingly, mutant strains were found to associate extremely low quantities of [S-methyl-3H]bleomycin A2, in contrast to normal strains that associated quite high amounts. However, the fractions of the total associated radioactivities that were released from normal and blm5-1 cells were equivalent. These results suggested that the extremely high killing suffered by blm5-1 mutant strains in response to bleomycin treatments results from something other than increased intracellular drug concentrations.

Alleles↗

Morphology of the vas deferens in an ethanol-drinking strain of rats (UChA and UChB).

Chronic alcoholism alters reproduction and therefore may be responsible for alterations of vas deferens, which are the subject of this analysis in UCh ethanol-drinking rats. The proximal and distal segments of the vas deferens of 20 animals were submitted to macroscopic, light microscopy, electron microscopy and morphometric analysis. The UCh rats showed atrophy of the epithelium of the vas deferens and alterations of the hypothalamus-pituitary axis. Ethanol induces changes in the epithelium of the vas deferens and hypothalamus-pituitary axis of UCh rats.

Alcohol Drinking↗

Determination of the virulence of the pigmentation-deficient and pigmentation-/plasminogen activator-deficient strains of Yersinia pestis in non-human primate and mouse models of pneumonic plague.

The current human plague vaccine, a killed Yersinia pestis whole-cell preparation, does not protect against aerosol challenge and is reactogenic and antigenically undefined. Live attenuated Y. pestis, such as pigmentation-deficient (Pgm-) strains, have been used frequently as vaccines and are efficacious. They are used widely in plague research and assumed to be safe. However, they can cause serious adverse reactions, and their aerosol infectivity is not known. We tested the virulence of a defined Pgm- variant of the C092 strain of Y. pestis in mouse and non-human primate models of pneumonic plague. The ten-fold lower median lethal dose by the aerosol compared to the subcutaneous (s.c.) routes of the Pgm- strain in mice suggested that the Pgm- strain might be less attenuated by the former than by the latter route. After exposure of 16 African green monkeys to inhaled doses ranging from 1.1 x 10(4) to 8.1 x 10(7)cfu, eight died and eight survived. The terminal cultures collected from five of the non-survivors were all positive for Y. pestis. Two of the remaining three non-survivors were culture-negative but had pathologic and immunologic evidence of infection with Y. pestis, specimens could not be obtained nor the cause of death determined for the third one. The deaths were not dose-related, and there were some differences in the pathology associated with infection by the Pgm- strain compared to the wild-type (wt) strain. However, the Pgm- derivative was clearly virulent for monkeys by the aerosol route. A mutant of the Pgm- strain, which has a deletion in the plasminogen activator (Pla) virulence locus (pla), appeared to be more attenuated than was either the Pgm- single mutant (in NHPs and mice) or the Pla- single mutant strain (in mice) and has potential as a live vaccine.

Administration, Inhalation↗

Protection by SIV VLP DNA prime/protein boost following mucosal SIV challenge is markedly enhanced by IL-12/GM-CSF co-administration.

The ever increasing number of people infected by human immunodeficiency virus (HIV) throughout the world renders the development of effective vaccines an urgent priority. Herein, we report on an attempt to induce and enhance antiviral responses using a deoxyribonucleic acid (DNA) prime/virus-like particles (VLP) protein boost strategy adjuvanted with interleukin (IL)-12/GM-CSF in rhesus macaques challenged with simian immunodeficiency virus (SIV). Thus, groups of monkeys were administered three consecutive doses of pVecB7 a plasmid expressing VLP with or without plasmids expressing IL-12 and GM-CSF at weeks 0, 13 and 26. The VLP boost was administered at week 39 with or without IL-12. All monkeys were challenged intrarectally with SIVsmE660 2 months following the protein boost. All except one immunized monkey became infected. While all immunized monkeys showed a marked reduction of acute viral peaks, reduction of viral load set points was only achieved in groups whose prime-boost immunizations were supplemented with IL-12/GM-CSF (prime) and/or with IL-12 (boost). Control of viremia correlated with lack of disease progression and survival. Detection of virus in rectal washes at 1 year post-challenge was only successful in monkeys whose immunizations did not include cytokine adjuvant, but these loads did not correlate with plasma viral loads. In summary, use of IL-12 and/or GM-CSF was shown to provide significant differences in the outcome of SIV challenge of prime/boost immunized monkeys.

Adjuvants, Immunologic↗

The -2 bp deletion in exon 6 of the 'alpha 7-like' nicotinic receptor subunit gene is a risk factor for the P50 sensory gating deficit.

Abnormality in the P50 auditory-evoked potential gating is an endophenotype associated with schizophrenia. Biochemical and genetic studies have suggested that the alpha 7 nicotinic acetylcholine receptor (nAChR) is involved in this sensory gating deficit. Two related alpha 7 genes (CHRNA7 and CHRNA7-like gene) resulting from a partial duplication (from exon 5 to exon 10) are present in the human genome. Two types of genetic variation, a large deletion and a -2 base-pair deletion in exon 6 resulting in a truncation of the open reading frame, affect specifically the CHRNA7-like gene. We developed a simple multiplex PCR assay on genomic DNA, allowing the quantification of the number of exons 6 and the distinction of all possible exon 6 genotypes. Genotyping of 70 schizophrenic patients and 77 controls showed that carrying at least one -2 bp deletion of exon 6 did not constitute a risk factor for schizophrenia. In contrast, the distribution of genotypes differed significantly between subjects with normal and abnormal P50 ratios, with an over-representation of genotypes carrying at least one -2 bp deletion of exon 6 among subjects exhibiting an abnormal P50 ratio. We thus conclude that the -2 bp deletion within the CHRNA7-like gene is a risk factor for P50 sensory gating deficit. Interestingly, most of the effect came from the non schizophrenic group, which may suggest that in schizophrenic patients other risk factors account for the large proportion of subjects exhibiting an abnormal P50 ratio.

Adult↗

Challenges associated with the evaluation of veterinary product bioequivalence: an AAVPT perspective.

The Generic Animal Drug Patent Term Restoration Act (GADPTRA) enacted in 1988 provided the same benefits to animal drug products that were granted to human generic products. It has been over 13 years since the GADPTRA was enacted, and veterinary drug sponsors and regulators have gained enormous insight and experience into some of the unique challenges associated with the determination of product bioequivalence for veterinary dosage forms. Moreover, advances in information and technology have opened both new issues that must be addressed and new mechanisms for demonstrating product bioequivalence. While many aspects of the existing Center for Veterinary Medicine Bioequivalence Guidance continue to provide invaluable guidance to the animal drug industry, there are also aspects of this guidance that are being called into question. Therefore, during the 2001 annual meeting of the American Academy of Veterinary Pharmacology and Therapeutics, participants were asked to address issues and concerns associated with the evaluation of veterinary product bioequivalence. This manuscript provides a summary of the concerns and discussions that transpired.

Animals↗

Kinetics of spermatogenesis in the Mongolian gerbil (Meriones unguiculatus).

The Mongolian gerbil (Meriones unguiculatus) is a small rodent native to the arid regions of Mongolia and Northeastern China. The present study provides descriptions of both the cellular associations of the seminiferous-epithelium cycle and relative frequencies of stages in the gerbil. Based on the development of the acrosomic system and the nuclear morphology changes using the PAS-H staining technique, the transformation of spermatids into spermatozoa was divided into 15 steps. The first 12 steps were used to identify 12 stages or cellular associations and the other three steps were spread among the first six stages of the cycle of the seminiferous epithelium. The relative frequencies found for stages I through XII were: 13.15; 8.06; 8.98; 6.48; 5.37; 6.71; 7.36; 7.45; 7.27; 5.83; 11.53 and 11.81, respectively. Stage I had the highest frequency while stage V proved the lowest frequency among the XII stages. The pattern of spermatogenesis is similar to those of rodents used as laboratory animals. The present description is the first for this rodent and provides the foundation for a variety of future studies of the testis in this animal.

Animals↗

Mapping brain response to social stress in rodents with c-fos expression: a review.

Social defeat is an important event in the life of many animals, and forms part of the process of social control. Adapting to social defeat is thus an intrinsic part of social "homeostasis", and mal-adaptation may have pathological sequelae. Experimental models of social defeat (e.g. inter-male aggression) have existed for many years. However, very few studies have investigated the changes in brain activity in male animals exposed to the social stress of being defeated by another conspecific male, and in all these studies the expression of the immediate-early gene c-fos has been used as the marker of neuronal activity. In general, the results obtained inform that many areas of the brain, especially those involved in the general stress response, increase their activity when animals are exposed to an acute defeat. However, when animals are defeated repeatedly over many consecutive days, the level of activation of the brain shows different patterns of adaptation depending on the brain areas (varying from complete habituation to persistent activation). Discrepancies between studies may be due to differences in the experimental procedure. On the other hand, further research has to be conducted in order to understand what these changes in the brain activity mean in relation to the other stress responses to social defeat. Furthermore, knowing that the corresponding protein products of many immediate-early genes are transcription factors that can promote or inhibit the expression of target genes, research following this approach is also necessary.

Animals↗

Efficacy of ravuconazole in treatment of systemic murine histoplasmosis.

Ravuconazole (RCZ) was evaluated for efficacy in comparison to fluconazole (FCZ) and itraconazole (ITZ) in murine models of disseminated histoplasmosis. All regimens tested prolonged survival (P < 0.05 to 0.0001). At equivalent doses of 50 mg/kg of body weight, RCZ and ITZ were equally effective and RCZ was more effective than FCZ (P = 0.02). Clearance of fungal burden from the livers and spleens of mice showed RCZ and ITZ at doses of 50 mg/kg to be efficacious but not curative. These data indicate that RCZ should be studied further.

Animals↗

Morphological effects on the hard palatine mucosa of Calomys callosus submitted to experimental chronic alcoholism.

The morphological effects of ethanol ingestion on the hard palatine mucosa of adult male Calomys callosus were observed. Twenty rodents were divided into two experimental groups: the control group received solid diet, Purina rat chow, and tap water ad libitum; the alcoholic group received the same solid diet and ethanol P.A. diluted 20% in water (v/v). After 270 days of treatment, all animals were sacrificed and the hard palatine mucosa were prepared for TEM and SEM methods. The epithelial cells of the alcoholic group showed some alterations like cytoplasmatic lipid droplets, pycnotic nucleus and increased mitochondrial size. The lamina propria also presented intense lipid droplets accumulation. The morphological changes suggested that chronic ethanol consumption was able to modify the integrity of the mucosa.

Alcoholism↗

Relationship between fibrinogen protein and fibrinogen function in postmyocardial infarction patients.

The present study investigates the association between increases in the concentration and function of plasma fibrinogen in two groups of patients with chronic ischemic heart disease (11 with recurrent ischemic events and 19 free of these episodes) and in 34 healthy controls. The fibrinogen function index (fibrinogen function per unit of fibrinogen protein) (FgFI) was used as a measure of the fibrinogen clotting potential. The prothrombin fragment 1+2 (F1+2) and thrombin-antithrombin (TAT) were used as procoagulant markers. Plasma sialic acid (SA) was also evaluated as an inflammatory marker. No differences were found between FgFI (1.06+/-0.13 vs. 1.02+/-0.13), F1+2 (1.2+/-0.5 vs. 1.1+/-0.4 nmol/l) and TAT (2.5+/-1.3 vs. 2.5+/-0.7 microg/ml) in postinfarction patients without recurrent coronary ischemic events and the control group. However, postinfarction patients who suffered recurrent coronary ischemic events had significantly higher FgFI than patients without these symptoms (1.19+/-0.09 vs. 1.06+/-0.13), P<.01) and than the control group (1.19+/-0.09 vs. 1.02+/-0.13, P<.001). Moreover, the F1+2 (1.4+/-0.5 vs. 1.1+/-0.4 nmol/l, P<.05) and TAT (3.6+/-3.3 vs. 2.5+/-0.7 microg/ml, P<.05) were significantly higher in patients who suffered recurrent coronary ischemic events than in the control group. However, F1+2 and TAT were not different between patients with and without these symptoms. The fibrinogen protein (Fg-protein) concentration and high molecular weight fibrinogen (HMW-Fg) levels were significantly higher in both postinfarction patient groups than in the control group and in postinfarction patients with recurrent coronary ischemic events than in postinfarction patients without these symptoms. The plasma SA levels were significantly increased in postinfarction patients with and without recurrent coronary ischemia as compared with the control group. A positive correlation was found between fibrinogen and SA levels (r=.5, P<.01). In conclusion, our study indicates that the procoagulant factors, among which we include fibrinogen, F1+2 and TAT play a very active role in recurrent ischemic events in postmyocardial infarction patients. High plasma concentrations of both fibrinogen and SA suggests that fibrinogen becomes elevated as a consequence of inflammatory processes. The FgFI as an indicator of clotting potential of fibrinogen appears to be associated with ischemic events in chronic coronary artery disease.

Adult↗