Revisiting the human seminiferous epithelium cycle.

STUDY QUESTION: Can all types of testicular germ cells be accurately identified by microscopy techniques and unambiguously distributed in stages of the human seminiferous epithelium cycle (SEC)? SUMMARY ANSWER: By using a high-resolution light microscopy (HRLM) method, which enables an improved visualization of germ cell morphological features, we identified all testicular germ cells in the seminiferous epithelium and precisely grouped them in six well-delimitated SEC stages, thus providing a reliable reference source for staging in man. WHAT IS ALREADY KNOWN: Morphological characterization of germ cells in human has been done decades ago with the use of conventional histological methods (formaldehyde-based fixative -Zenker-formal- and paraffin embedding). These early studies proposed a classification of the SEC in six stages. However, the use of stages as baseline for morphofunctional evaluations of testicular parenchyma has been difficult because of incomplete morphological identification of germ cells and their random distribution in the human SEC. STUDY DESIGN, SIZE, DURATION: Testicular tissue from adult and elderly donors with normal spermatogenesis according to Levin's, Johnsen's and Bergmann's scores were used to evaluate germ cell morphology and validate their distribution and frequency in stages throughout human spermatogenesis. PARTICIPANTS/MATERIALS, SETTING, METHODS: Testicular tissue from patients diagnosed with congenital bilateral agenesis of vas deferens (n = 3 adults) or prostate cancer (n = 3 elderly) were fixed in glutaraldehyde and embedded in araldite epoxy resin. Morphological analyses were performed by both light and transmission electron microscopy. MAIN RESULTS AND THE ROLE OF CHANCE: HRLM method enabled a reliable morphological identification of all germ cells (spermatogonia, spermatocytes and spermatids) based on high-resolution aspects of euchromatin, heterochromatin and nucleolus. Moreover, acrosomal development of spermatids was clearly revealed. Altogether, our data redefined the limits of each stage leading to a more reliable determination of the SEC in man. LIMITATIONS, REASONS FOR CAUTION: Occasionally, germ cells can be absent in some tubular sections. In this situation, it has to be taken into account the germ cell association proposed in the present study to classify the stages. WIDER IMPLICATIONS OF THE FINDINGS: Our findings bring a new focus on the morphology and development of germ cells during the SEC in human. Application of HRLM may be a valuable tool for research studies and clinical andrology helping to understand some testicular diseases and infertility conditions which remain unsolved. STUDY FUNDING/COMPETING INTEREST: Experiments were partially supported by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Fundação de Amparo à Pesquisa de Minas Gerais (FAPEMIG) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). The authors declare that there are no conflicts of interest. TRIAL REGISTRATION NUMBER: Not applicable.

Randomized, double-blind, sham-controlled trial to evaluate the efficacy and tolerability of electroconvulsive therapy in patients with clozapine-resistant schizophrenia.

There is no established treatment for patients with clozapine-resistant schizophrenia (CRS). Clozapine augmentation strategies with antipsychotics or others substances are effective in comparison with placebo while and Electroconvulsive therapy (ECT) showed to be effective in comparison with treatment as usual (TAU) but not with placebo (sham-ECT). In the present double- blind randomized controlled trial, we compared 40 outpatients who received 20 sessions of ECT (n = 21) or sham-ECT (n = 19) (age = 37.40 ± 9.62, males = 77.5 %, illness duration = 14.95 ± 8.32 years, mean total Positive and Negative Syndrome Scale (PANSS) = 101.10 ± 24.91) who fulfilled well-defined CRS criteria including baseline clozapine plasma levels ≥350 ng/mL. The primary outcome was the ≥50 % PANSS Total Score reduction; secondary outcomes were the scores of the PANSS subscales, PANSS five-factor dimensions, PANSS-6 and the Calgary Depression Rating Scale (CDRS). Treatment response was analyzed by percentage reduction, Linear Mixed Models and effect sizes. At baseline both groups showed no differences except for years of school education (included as a covariate). At endpoint, only 1/19 of the completers (5.26 %) in the ECT group and 0/17 in the sham-ECT group showed a ≥50 % total PANSS score reduction. Both groups showed no significant differences of the total PANSS score (F = 0.12; p = 0.73), Positive (F = 0.27, p = 0.61), Negative (F = 0.25, p = 0.62), and General Psychopathology scores (F = 0.01, p = 0.94) as well for all PANSS five factors, the PANSS-6 and CDRS. Thus, the present study found no evidence that ECT is better than Sham-ECT in patients with CRS. Future sham-ECT controlled studies with larger sample sizes are warranted to test the efficacy of ECT for patients with CRS.

Exposure to Pfaffia glomerata causes oxidative stress and triggers hepatic changes.

Medicinal plant species are genetically engineered to obtain higher production of biomass and specific secondary metabolites, which can be used in the pharmaceutical industry. The aim of the present study was to evaluate the effect of Pfaffia glomerata (Spreng.) Pedersen tetraploid hydroalcoholic extract on the liver of adult Swiss mice. The extract was prepared from the plant roots and given to the animals by gavage, for 42 days. The experimental groups were treated with water (control), Pfaffia glomerata tetraploid hydroalcoholic extract (100, 200 and 400 mg/kg) and Pfaffia glomerata tetraploid hydroalcoholic extract discontinuously (200 mg/kg). The last group received the extract every 3 days, for 42 days. The oxidative status, mineral dynamics, and cell viability were analysed. The liver weight and the number of viable hepatocytes were reduced, despite the increased cell's number. Increased levels of malondialdehyde and nitric oxide, and changes in iron, copper, zinc, potassium, manganese and sodium levels were observed. aspartate aminotransferase levels were increased while alanine aminotransferase levels were decreased due to BGEt intake. Our results showed that BGEt induced alterations of oxidative stress biomarkers leading to liver injury, which was associated with a reduction in the number of hepatocytes.

Seroprevalence of Toxocara infection in children and environmental contamination of urban areas in Paraná State, Brazil.

The objectives of this study were to evaluate the contamination by eggs of Toxocara in sandy areas or grass lawns of outdoor recreation areas that are used by children, and the frequency of seroprevalence in children, from three cities of fewer than 45,000 inhabitants in Paraná, Brazil. From May 2005 to December 2007, five samples were taken from each of 13 sandy sites and 18 grass lawns, all from plazas and public schools. Blood samples from children aged 0-12 years were analysed by immunoassay for anti-Toxocara IgG. The soil samples were processed by floatation and sedimentation. Eggs of Toxocara spp. were present in 44.7% (38/85) of the samples from grassed areas and in 21.4% (15/70) of the sand samples. The lawns were 2.16 times more contaminated than the sand (P = 0.0009). However, the epidemiological variables showed no statistically significant difference between seropositive (36.8%; 130/353), and seronegative children. The rate of seropositivity was higher in children aged 0-5 years (P = 0.03), who were 1.94 times more likely to develop persistent wheezing (P = 0.02).

How bad is brazilian ginseng extract for reproductive parameters in mice?

Properties attributed to the Panax ginseng are also attributed to the Brazilian ginseng, such as adaptogenic and aphrodisiac effects. There are studies demonstrating that the Brazilian ginseng (BGE) possibly increases the serum levels of testosterone and nitric oxide in mice and rats. The present study aimed to evaluate the effects of its extract on male fertility and sperm quality. Male Swiss mice (n = 60) were divided into six groups. The control animals were provided 0.5 mL of water, and 0.5 mL of water containing 7 mg/kg per day (d) sildenafil citrate. Other animals were treated with BGE at 100 mg/kg/d, 200 mg/kg/d, and 400 mg/kg/d by gavage for 42 days. Finally, animals from the last group received 200 mg/kg BGE every 3 days (3-3d) by gavage for 42 days. The results showed a reduction in the number of resistant spermatids in the testis and damage to daily sperm production, culminating in a reduction in the number of epididymal spermatozoa. Although the sperm quality decreased in all experimental animals, only males treated with BGE 100 mg/kg/d showed pre and post implantation embryo losses. We concluded that BGE alters sperm viability compromising the embryonic development after implantation.

Transmission of Oropouche virus from man to hamster by the midge Culicoides paraensis.

Oropouche virus (arbovirus family Bunyaviridae, Simbu serological group) was experimentally transmitted from man to hamster by the bite of the midge Culicoides paraensis. Infection rates and transmission rates were determined after the midge had engorged on patients with viremia. The threshold titer necessary to enable infection or transmission by the midges was approximately 5.3 log10 of the median lethal dose of the virus in suckling mice per milliliter of blood. Transmission was achieved 6 to 12 days after C. paraensis had taken the infective blood meal. This represents conclusive evidence of transmission of an arbovirus of public health importance to man by a member of the Ceratopogonidae family.

Environmental insights from high-resolution (SIMS) sulfur isotope analyses of sulfides in Proterozoic microbialites with diverse mat textures.

In modern microbial mats, hydrogen sulfide shows pronounced sulfur isotope (δ34 S) variability over small spatial scales (~50‰ over <4 mm), providing information about microbial sulfur cycling within different ecological niches in the mat. In the geological record, the location of pyrite formation, overprinting from mat accretion, and post-depositional alteration also affect both fine-scale δ34 S patterns and bulk δ34 Spyrite values. We report µm-scale δ34 S patterns in Proterozoic samples with well-preserved microbial mat textures. We show a well-defined relationship between δ34 S values and sulfide mineral grain size and type. Small pyrite grains (<25 µm) span a large range, tending toward high δ34 S values (-54.5‰ to 11.7‰, mean: -14.4‰). Larger pyrite grains (>25 µm) have low but equally variable δ34 S values (-61.0‰ to -10.5‰, mean: -44.4‰). In one sample, larger sphalerite grains (>35 µm) have intermediate and essentially invariant δ34 S values (-22.6‰ to -15.6‰, mean: -19.4‰). We suggest that different sulfide mineral populations reflect separate stages of formation. In the first stage, small pyrite grains form near the mat surface along a redox boundary where high rates of sulfate reduction, partial closed-system sulfate consumption in microenvironments, and/or sulfide oxidation lead to high δ34 S values. In another stage, large sphalerite grains with low δ34 S values grow along the edges of pore spaces formed from desiccation of the mat. Large pyrite grains form deeper in the mat at slower sulfate reduction rates, leading to low δ34 Ssulfide values. We do not see evidence for significant 34 S-enrichment in bulk pore water sulfide at depth in the mat due to closed-system Rayleigh fractionation effects. On a local scale, Rayleigh fractionation influences the range of δ34 S values measured for individual pyrite grains. Fine-scale analyses of δ34 Spyrite patterns can thus be used to extract environmental information from ancient microbial mats and aid in the interpretation of bulk δ34 Spyrite records.

Relationship between invertebrate fauna and bromeliad size.

Several bromeliads species store water and organic substrates, allowing the establishment of phytotelmata and associated fauna on their leaves. In this study, we sampled 70 individuals of Vriesea sp. (Carrière) (Bromeliaceae), in rupestrian fields in the Serra de Ouro Branco-MG, Brazil. The relationships between invertebrate species richness and abundance and size of bromeliads were tested using multiple regression. We found 19 species associated with bromeliads, mainly Diptera larvae. The abundance of the phytotelmate fauna increased principally in relation to the volume of water in the bromeliad reservoir. Phytotelmata richness was affected principally by diameter of the reservoir. There was a significant relationship between the abundance and richness of invertebrates associated with leaves with diameter and height of the plant. Invertebrate richness was better explained by abundance of individuals. These results suggest that the increase of richness was attended by higher numbers of microhabitats and more space for colonization of bigger bromeliads. Additionally, there was more chance of sampling different species in locales with greater abundance of individuals.

Rediscovering hermaphroditism in Grammatidae with the description of the testicular gland in Brazilian Basslet Gramma brasiliensis.

Many aspects of sex change in reef fishes have been studied, including behavior and social organization. However, gonad histology remains the most robust way to identify sexual patterns in fishes. Some uncommon tissues remain poorly described, such as the accessory gonadal structures found in species from the Gobiidae family, which are rare in other bony fishes. This is the first report of the testicular gland in Gramma brasiliensis and for the Grammatidae family. Between April 2011 and February 2012 eighty specimens were collected during four dive campaigns on the Taipus de Fora reef (13°56'20"S 38°55'32"W), Bahia, Northeast Brazil, and their sex was determined. Thirteen per cent of the active-females and 90% of the active-males had testicular gland tissue in their ovotestis. This discovery led to additional research into the characteristics of the gland tissue and its relationship with gonadal maturation. Three patterns of testicular gland development were found in Brazilian basslet ovotestis. Both ova and sperm-producing gonad contained testicular gland tissue, and the appearance of this tissue seems to be the first modification of ovotestis tissue marking the beginning of the protogynous sex-change process in G. brasiliensis.

Microinjection of metallothionein-oncomodulin DNA into fertilized mouse embryos is correlated with fetal lethality.

Oncomodulin (ONCO) is an oncodevelopmental protein expressed in placental and extraembryonic tissue and re-expressed in a wide variety of tumors. The metallothionein promoter (MT) is active in numerous adult tissues, in parietal and visceral extraembryonic endoderm, and developing liver. To study the function of oncomodulin we microinjected MT-ONCO DNA into one-cell embryos and examined tissues of fetal and adult mice. Analysis of implant sites from embryos, microinjected with MT-ONCO DNA then placed into pseudopregnant females, indicated a greater than three-fold increase in empty and necrotic implant sites relative to SV2NEO-microinjected embryos and a seven-fold rise relative to non-microinjected embryos. The striking feature of the lethality was the presence of a normal placenta but absence of fetal tissue. Few MT-ONCO DNA transgenic mice were isolated (3.5%) and none were able to express oncomodulin protein or RNA in any tissue examined, even after prolonged heavy metal stimulation of the MT promoter. Fetal mortality is best correlated with expression of oncomodulin causing an interruption of either cellular differentiation or organogenesis before day 9 in development.

Polyomavirus large T-antigen expression in heart of transgenic mice causes cardiomyopathy.

One of the early genes of polyomavirus, large T-antigen (PVLT), has been classified in vitro as an immortalizing gene. In order to determine the ability of PVLT to cause the formation of hyperplasia or tumors in vivo, we generated transgenic mice harboring the cDNA for PVLT linked to the heavy-metal responsive metallothionein-1 promoter (MT). The transgene was primarily expressed in testes and seminal vesicles, but expression was also detected in heart of a single transgenic line. The expression of the transgene in the heart of MT-PVLT line 8 mice was correlated with cardiomyopathy and atrial thrombus formation leading to premature death at approximately 160 days due to cardiac failure. The heart of affected animals was from 1.5 to 5.2 fold greater in weight and 2 fold greater in dimensions than normal nontransgenic mice. Affected hearts fell short of frank tumor phenotype and no macroscopic nor microscopic focal growth was found. Histologically the heart has a heterogenous cardiomyocyte population with markedly enlarged cells mixed with relatively normal cells. Both cell types express PVLT protein. The primary cell type affected is the cardiomyocyte however, as heart proportions are maintained, interstitial and non-myocyte cells must be affected either directly or indirectly. Expression of PVLT has upset normal strict control of cell growth in these hearts to result in a new model of congestive cardiomyopathy.

A correlated morphological and biochemical study on the rat adrenal steroidogenesis.

The ultrastructural and biochemical alterations produced by an hypocholesterolemic drug, 17 alpha-ethinyl estradiol, on the rat adrenal cortex were studied. Male rats aged two months and with approximately 200 g in weight were injected subcutaneously with 10 mg/kg/day of ethinyl estradiol during 9 days; rats injected with 1 ml propylene glycol were used as controls. The animals were sacrificed on the 10th day, and the adrenals from some of them were processed for electron microscopy. The adrenals from the remaining rats were used for measurements of the glands cholesterol and corticosterone, which were also measured in the blood. In estradiol-treated rats the zona fasciculata cells exhibited numerous microvilli, increase in the size of mitochondria and decrease in the number of lipid droplets. The quantitative analysis showed a significant increase of the volumetric density of mitochondria and microvilli and a significant decrease of the lipid droplets in the treated rats, when compared with normal ones. In treated rats, the concentration of cholesterol and corticosterone in the gland and blood were significantly decreased. These data show that hypocholesterolemia produced by estradiol has a remarkable effect on adrenal steroidogenesis, depletes the pool of adrenal cholesteryl esters, and evidences the role of plasma cholesterol in the corticosteroidogenesis.

Chagas' disease diagnosis: comparative analysis of parasitologic, molecular, and serologic methods.

During the course of chronic chagasic infection, low parasitemia levels prevent parasite detection by current techniques such as hemoculture and xenodiagnosis. Since serologic tests have sensitivity but lack specificity, molecular assays based on the polymerase chain reaction (PCR) have been proposed as alternative tools for parasite detection in individuals with chronic Chagas' disease. A variable degree of PCR efficiency has been reported in the literature and illustrates the need for further evaluation of large numbers of chagasic patients. In this study, we compared an optimized PCR technique with hemoculture and complement-mediated lysis (CoML) in 113 individuals from or living in endemic areas of Brazil who had conventional serologic results that were either positive, negative, or inconclusive. The PCR amplification yielded positive results in 83.5% (66 of 79) of individuals with positive serology, 47.6% (10 of 21) with negative serology, and 46.2% (6 of 13) with inconclusive serology. Of 10 patients with negative serology and positive PCR result, eight (80%) had positive CoML, indicating that they could have been chagasic but were not mounting immune responses. The PCR results were also positive for all individuals who had positive hemoculture, for 37 individuals with negative hemoculture and positive serology, and for two of six individuals with inconclusive serology and negative hemoculture. Thirteen individuals living in nonendemic areas who had negative serology were used as a negative control group: 100% had negative PCR results. Our results show that the optimized PCR protocol used here was very sensitive in detecting the presence of Trypanosoma cruzi in chronic chagasic patients. The PCR and CoML results were well correlated in all of the groups studied, which suggests that our PCR protocol may be effective in the evaluation of cure in patients who receive anti-parasite treatment.

Oropouche virus. IV. Laboratory transmission by Culicoides paraensis.

Biological transmission of Oropouche (ORO) virus by Culicoides paraensis (Goeldi) has been successfully demonstrated in the laboratory. Adult Culicoides, collected in an area where ORO virus was absent, were infected by feeding on viremic hamsters and then periodically exposed to susceptible hamsters at specific intervals post-infectious blood meal. These C. paraensis were capable of biological transmission of the virus 4-9 days post-feeding on viremic hamsters circulating 6.7-9.9 log10SMLD50/ml virus. Infection rates of 54% and 80% were found for C. paraensis assayed 7 days post-feeding. Virus transmission rates for these experiments were 83% and 25%, respectively. No evidence of mechanical transmission of ORO virus by C. paraensis was observed when interrupted feeding of Culicoides on viremic hamsters was followed by feeding on susceptible hamsters.

Household epidemiology of Entamoeba histolytica infection in an urban community in northeastern Brazil.

The natural history of infection with Entamoeba histolytica was studied in 2 slum communities in northeastern Brazil. Twenty-eight index patients colonized with E. histolytica were identified. Three stool specimens from the index patients and their household contacts were gathered over a 45-day period and tested for E. histolytica by means of a specific enzyme-linked immunosorbent assay-based detection kit. The detection kit is an antigen capture assay that has been shown to be highly specific for E. histolytica and does not detect nonpathogenic Entamoeba dispar or other enteric organisms. Blood samples were also collected at the start of the study, at 45 days, and at 6 months and analyzed for E. histolytica-specific antibody. High rates of colonization were seen in the family units. Colonization was self-limited, with 85% of colonized patients clearing their infections within 45 days. Reinfection appeared to be low during this time; however, previous seropositivity did not prevent colonization.

Efficacy of artesunate plus chloroquine for uncomplicated malaria in children in Sao Tome and Principe: a double-blind, randomized, controlled trial.

We conducted a double-blind, randomized, placebo-controlled trial in Sao Tome and Principe to investigate the safety, tolerability and efficacy of chloroquine (CQ) combined with artesunate (AS) over CQ monotherapy. Four hundred children, aged 6-59 months, with acute uncomplicated Plasmodium falciparum malaria were randomized to receive a standard dose of CQ (25 mg/kg bodyweight) over 3 d or CQ + AS (4 mg/kg bodyweight) daily for 3 d. Children were followed-up for 28 d. The combined treatment was well tolerated and there were no serious drug-related adverse events. By day 2 parasite clearance was significantly faster for children treated with CQ + AS compared with CQ alone (29/194 [14.9%] vs. 168/190 [88.4%] still parasitaemic, P< 0.0001). Day 14 parasitological failure rates were 153/191 (80.1%) for CQ alone compared with 32/193 (16.6%) in the CQ + AS group (odds ratio [OR] =20.2, 95% CI 11.7-35.4, P< 0.001). Corresponding clinical failure rates were 128/161 (67.0%) and 12/193 (6.2%) (OR = 30.6, 95% CI 15.3-62.7, P< 0.001). By day 28 the parasitological failure rates (new infections excluded) were 155/191 (81.1%) in the CQ group and 63/194 (32.4%) in the CQ + AS group (OR = 8.9, 95% CI 5.4-14.7, P< 0.001). Symptoms resolved faster in children who received AS. They were also less likely to be gametocytaemic after treatment. The combination treatment was well tolerated and considerably improved treatment efficacy. However, the current levels of CQ resistance preclude its use in Sao Tome where CQ should be abandoned as first-line drug. However, CQ + AS may be an option in areas where CQ resistance is lower.

Genetic relationships between Trypanosoma cruzi strains isolated from chronic chagasic patients in southern Brazil as revealed by RAPD and SSR-PCR analysis.

30 Trypanosoma cruzi strains isolated from chronic chagasic patients were studied at the genotype level by RAPD with arbitrary primers and SSR-PCR analysis. The genetic distance of strains was measured by the percentage of unshared bands. The results showed that the strains isolated from chronic patients from different Chagas' disease endemic areas of Brazil constituted a broad group significantly more correlated than reported in previous studies, presenting RAPD profiles with an average of 71% of shared bands and SSR-PCR patterns with a mean of 59% of shared bands. In contrast to other findings in the literature, these strains did not group on the basis of their geographic origin. These results suggest that a special adaptation of a parasite population in human hosts from mixed infective T. cruzi populations circulating in nature may have occurred.

Model to evaluate the toxic effect of drugs: vincristine effect in the mass of organs and in the distribution of radiopharmaceuticals in mice.

There are evidences that the biodistribution of radiopharmaceuticals can be modified by some drugs. As chemotherapeutic drugs present important toxic effects, we studied the vincristine effect in the mass of organs and are trying to develop a model to evaluate the action of chemotherapeutic drug using the biodistribution of radiopharmaceuticals. Vincristine was administered (n=15) into female Balb/c mice, the organs isolated and their mass determined. To study the vincristine effect in the biodistribution of technetium-99m-dimercaptosuccinic acid (99mTc-DMSA) or technetium-99m-diethylenetriaminepentaacetic acid (99mTc-DTPA), vincristine (0.03 mg) was administered in the animals (n=15) in three doses. 99mTc-DMSA or 99mTc-DTPA was injected 1h after the last dose. After 0.5h, the animals were sacrificed and the percentage of radioactivity (%ATI) and the percentage of radioactivity per gram of tissue (%ATI/g) in each organ were calculated. The results have shown that the mass decreased significantly (Wilcoxon test, P<0.05) in thymus, spleen, ovary, uterus, kidneys, pancreas. The %ATI to 99mTc-DMSA increased in lung, pancreas, heart, thyroid, brain, and bone, and the %ATI/g increased in uterus, ovary, spleen, thymus, kidney, lung, liver, pancreas, heart, thyroid, brain and bone. To 99mTc-DTPA, the %ATI increased in uterus, ovary, spleen, thymus, kidney, lung, liver, stomach, heart and bone, and the %ATI/g increased in uterus, ovary, spleen, thymus, kidney, lung, liver, stomach, heart and bone. The results were statistically significant (Wilcoxon test). The results can be explained by the metabolization, therapeutic, toxicological or immunosupressive action of the vincristine. This model, probably, should be used to evaluate the toxic effect of various drugs.

Effect of an extract of cauliflower (leaf) on the labeling of blood elements with technetium-99m and on the survival of Escherichia coli AB1157 submitted to the treatment with stannous chloride.

The labeling of red blood cells (RBC) with technetium-99m (99mTc) depends on a reducing agent and stannous chloride (SnCl(2)) and is widely utilized. This labeling may also be altered by drugs, and SnCl(2) reduces the survival of Escherichia coli cultures. Cauliflower (Brassica oleracea L. var. botrytis) is used in folk medicine and we evaluated its influence on (i) the labeling of blood elements with 99mTc, and (ii) on the survival of an E. coli strain. Blood was withdrawn from rats that drank the extract of cauliflower (15 days). Blood was incubated with SnCl(2) and with 99mTc, as sodium pertechnetate, centrifuged and plasma (P) and RBC were isolated. Samples of P and RBC were also precipitated, centrifuged and soluble and insoluble fractions isolated. E. coli culture was treated with SnCl(2) in the presence of cauliflower. The extract of cauliflower did not alter the fixation of 99mTc on blood fractions; however, it abolished the lethal effect of SnCl(2) on the E. coli culture. We suggest that the substances present in the extract of cauliflower probably, would have redox property with different mechanisms of action. The oxidant action of the substances of the extract would not be strong enough to oxidise the stannous ions altering the 99mTc-labeling. However, the referred substances could oxidise these ions sufficiently to protect the E. coli culture against the lethal effect of the stannous ion.

Assessment of the effect of vincristine on the biodistribution of 99Tcm-labelled glucoheptonic acid in female Balb/c mice.

There is evidence that the biodistribution and the pharmacokinetics of 99Tcm radiopharmaceuticals can be modified by some drugs, pathological states, irradiation and surgical procedures. Vincristine have been widely used in various chemotherapeutic protocols in oncology. We are trying to develop an animal model to assess the toxicology in different organs of compounds used as therapeutic drugs. We have studied the effect of vincristine on the distribution of 99Tcm-glucoheptonic acid (99Tcm-GHA) in female mice. After the last dose of vincristine, 99Tcm-GHA (7.4 MBq) was injected, the animals sacrificed and the percentage of radioactivity determined in the isolated organs. The percentage of activity was significantly decreased in the uterus, ovary, spleen, thymus, lymph nodes (inguinal and mesenteric), kidney and heart, but was not significantly altered in the lung, liver, pancreas, stomach, thyroid, brain and bone. Our results can be explained by the metabolic, toxic, therapeutic and immunosuppressive actions of this chemotherapeutic drug.