Ontogenetic and sexual differences in the venom of Bothrops moojeni: insights from a litter and its mother.

Variability in snake venom composition is well-documented and crucial for understanding snake ecology and predicting snakebites. In this study, we characterize the venom composition and biological activities of newborn female and male Bothrops moojeni and their mother. Our results reveal significant differences between the venom of newborn females and males, demonstrating a broad and diverse range of proteins. The venoms of newborn females showed higher serine protease effects, increased hemorrhagic activity, and greater lethality compared to the venom of newborn males. However, no differences were observed in phospholipase A2 and coagulant activity. The differences in protein composition and toxic activities between maternal and neonatal venom, as well as between the venoms of newborn females and males, contribute to understanding the diverse outcomes of snakebites. These results underscore the importance of considering sex and ontogeny in understanding venom composition in snakes.

The invasive giant African land snail, Achatina fulica (Gastropoda: Pulmonata): global geographical distribution of this species as host of nematodes of medical and veterinary importance.

The giant African land snail, Achatina fulica, is an important invasive species in many countries, where it causes losses in biodiversity and agriculture, as well as impacting the health of both humans and animals, as the intermediate host of medically important nematodes. The present study is based on a comprehensive review of the literature on the nematodes that have been found in association with A. fulica, worldwide. We searched a number of different databases and used the findings to investigate the methods used to extract and identify the nematodes, their larval stages, and environment and collecting procedures of the infected molluscs. Between 1965 and 2021, 11 nematode species were recorded in association with A. fulica in 21 countries. Most of the studies recorded associations between A. fulica and Angiostrongylus cantonensis, which causes cerebral angiostrongyliasis in humans and Aelurostrongylus abstrusus, which provokes pneumonia in felines. The nematodes were extracted primarily by artificial digestion with hydrochloric acid or pepsin, and identified based on their morphology or through experimental infection to obtain the adult. In most cases, the nematodes were at larval stage L3, and the infected A. fulica were collected from anthropogenic environments. The results demonstrate the importance of A. fulica as a host of nematodes of medical and veterinary importance, as well the contribution of anthropogenic environments to the occurrence of the parasites, and give information about the different methods used to collect and identify the nematodes found associated with this species.

Behavioral and morphological effects of resveratrol and curcumin in rats submitted to doxorubicin-induced cognitive impairment.

Doxorubicin (DOX) is known to cause cognitive impairments in patients submitted to long-term chemotherapy (deficits also known as chemobrain). Therefore, there is an urgent need for therapeutic strategies capable of returning cancer survivors back to their previous quality of life. The present study investigated whether resveratrol (RSV) or curcumin (CUR) administration could affect mnemonic function and brain morphological changes following DOX administration in rats. Male Wistar rats were divided into 4 groups: DOX group (2.5 mg/kg/week for 4 weeks, i.p., plus distilled water for 28 days, oral gavage - OG), DOX + RSV group (DOX, 2.5 mg/kg/week for 4 weeks, i.p., plus RSV, 10 mg/kg/day for 28 days, OG), DOX + CUR group (DOX, 2.5 mg/kg/week for 4 weeks, i.p., plus CUR, 100 mg/kg/day for 28 days, OG) and control (CTR) group (0.9% saline solution weekly for 4 weeks, i.p., plus distilled water for 28 days, OG). Behavioral analyses (open field - OF - and the novel object recognition test - NORT) were performed. Brains were collected and analyzed by hematoxylin-eosin and luxol fast blue staining techniques and by immunohistochemistry for GFAP (glial fibrillary acidic protein) expression in astrocytes and Iba1 (ionized calcium-binding adaptor molecule 1) expression in microglia. DOX-injected rats presented short-term and long-term memory impairments as seen in the NORT at 3 and 24 h after habituation and increased GFAP and Iba1 expression, respectively, in astrocytes and microglia of the frontal cortex, hypothalamus and hippocampus. Such cognitive deficits were prevented by CUR at both periods and by RSV at 24 h. DOX-induced astrogliosis and microgliosis were avoided by RSV and CUR. No signs of demyelination or neuronal loss were found in any group. Thus, CUR and RSV prevented memory loss, astrogliosis and microgliosis induced by DOX monotherapy.

Mini review - The role of Glucocerebrosidase and Progranulin as possible targets in the treatment of Parkinson's disease.

As per recent reports, there is an association between glucocerebrosidase (Gcase) enzyme and Parkinson's disease (PD). In addition, certain mutations in the Gcase gene (GBA) and the progranulin (PGRN) gene are found to be linked with the imbalance in the levels of Gcase enzyme. This imbalance or decrease or impairment in Gcase activity can lead to Gaucher disease, frontotemporal lobar degeneration (FTLD), dementia, etc. Recent evidences suggest that the drugs used to treat these diseases can be used for PD. The present review has focused on the therapeutic approaches used for diseases linked with Gcase enzyme, which can be used for PD. The review also considered possible target specific novel strategies, which may help to meet the unmet needs in the treatment of PD.

Prenatal LPS induces sickness behaviour and decreases maternal and predatory behaviours after an LPS challenge.

Purpose: The influence of a challenge dose of lipopolysaccharide (LPS) on the behavioural selection between maternal (MB) and predatory behaviours (PB) of female rats prenatally treated with the same endotoxin or saline solution (F1 generation) were studied.Material and methods: Thus, in adult age, these female rats were mated and, at lactation days 5 or 6, the following groups were formed: (1) LPS + LPS group-female rats prenatally treated with LPS and received an LPS challenge dose; (2) S + LPS group-female rats prenatally treated with saline solution and received a challenge LPS dose (3) S + S group-females rats prenatally treated with saline which received a saline injection. MB, PB to cockroaches, exploratory behaviour, periaqueductal grey (PAG) expression of the astrocytic biomarker glial fibrillary acidic protein (GFAP), and corticosterone and TNF-alpha serum levels were evaluated.Results: Showed that: (1) relative to the S + S group, the LPS + S group showed decreased MB and slightly increased PB, without inducing sickness behaviour; (2) the LPS + LPS group showed decreased MB but few effects on PB; (3) there was increased sickness behaviour associated with increased TNF-alpha serum levels in the LPS + LPS group; (4) a significant increase in GFAP expression was observed in both LPS groups, which was greater in the LPS + LPS group and (5) no differences in the corticosterone of all groups.Conclusions: Prenatal LPS impaired the switch from MB to PB in female rats of the LPS + LPS group by increased sickness behaviour as well as an increase in plasmatic TNF-alpha levels inducing PAG astrogliosis.

Human leukocyte antigen distribution and genomic ancestry in Brazilian patients with sickle cell disease.

Hematopoietic stem-cell transplantation (HSCT) is currently the only established curative treatment for sickle cell disease (SCD), but is limited by donor availability. Ethnicity is thought to have an impact on the complications experienced by patients that undergo HSCT and on the likelihood of identifying an human leukocyte antigen (HLA) matched donor. In the present study, we investigated the genomic ancestry and the distribution of HLA allele groups in Brazilian patients with SCD, compared these HLA profiles to worldwide populations and evaluate the availability of HLA-matched donors. A broad intercontinental admixture of patients with SCD was observed, with African ancestry ranging from 6.7% to 93.4%. In a dendrogram based on HLA frequencies, Brazilian patients with SCD were included in a branch containing only populations with a significant African component. Among the 126 patients evaluated, 10 (8%) found a HLA-matched unrelated donor in a database of 18 134 donors. Self-reported white, brown and black matched donors were identified, and no significant difference in the percentage of compatible donors was observed between these ethnic groups. Our results show that Brazilian patients with SCD are very admixed, indicating that this group is a promising target for admixture mapping of genes involved in complications after HSCT. Additional studies may help to clarify the impact of the genetic diversity and admixture of these patients on the donor availability.

Karyomorphology and karyotype asymmetry in the South American Caesalpinia species (Leguminosae and Caesalpinioideae).

With the purpose of addressing the pattern of karyotype evolution in Caesalpinia species, chromosome morphology was characterized in five species from Brazil, and karyotypic asymmetry was analyzed in 14 species from South America. All accessions had the chromosome number 2n = 24, which was first described here for Caesalpinia laxiflora Tul. and Cenostigma macrophyllum Tul. The karyotype formula of C. laxiflora, Caesalpinia pyramidalis Tul., and C. macrophyllum was 12 m. The formula varies amongst the populations of Caesalpinia bracteosa Tul. (11 m + 1 sm) and Caesalpinia echinata Lam. (10 m + 2 sm and 9 m + 3 sm). The intra- and interspecific variations in chromosome length were significant (analysis of variance, P < 0.05). Analyzing the asymmetry index (AI), revealed that Caesalpinia calycina Benth. had the most asymmetrical karyotype (AI = 10.52), whereas Caesalpinia paraguarienses (D. Parodi) Burkat. and Caesalpinia gilliesii (Hook.) Benth. had the most symmetrical karyotypes (AI = 0.91 and 1.10, respectively). There has been a trend to lower AI values for the Caesalpinia s.l. species assigned in Libidibia and intermediate values for those combined into Poincianella. On the other hand, the karyotypes of Erythrostemon species had extremely different AI values. This study confirms the existence of karyotype variability in Caesalpinia s.l. while revealing a possible uniformity of this trait in some of the new genera that are being divided from Caesalpinia s.l. More broadly, the 2n = 24 chromosome number is conserved. Metacentric chromosomes and low AI values predominate among Caesalpinia s.l. and Cenostigma.

Mercury toxicity in the Amazon: contrast sensitivity and color discrimination of subjects exposed to mercury.

We measured visual performance in achromatic and chromatic spatial tasks of mercury-exposed subjects and compared the results with norms obtained from healthy individuals of similar age. Data were obtained for a group of 28 mercury-exposed subjects, comprising 20 Amazonian gold miners, 2 inhabitants of Amazonian riverside communities, and 6 laboratory technicians, who asked for medical care. Statistical norms were generated by testing healthy control subjects divided into three age groups. The performance of a substantial proportion of the mercury-exposed subjects was below the norms in all of these tasks. Eleven of 20 subjects (55%) performed below the norms in the achromatic contrast sensitivity task. The mercury-exposed subjects also had lower red-green contrast sensitivity deficits at all tested spatial frequencies (9/11 subjects; 81%). Three gold miners and 1 riverine (4/19 subjects, 21%) performed worse than normal subjects making more mistakes in the color arrangement test. Five of 10 subjects tested (50%), comprising 2 gold miners, 2 technicians, and 1 riverine, performed worse than normal in the color discrimination test, having areas of one or more MacAdam ellipse larger than normal subjects and high color discrimination thresholds at least in one color locus. These data indicate that psychophysical assessment can be used to quantify the degree of visual impairment of mercury-exposed subjects. They also suggest that some spatial tests such as the measurement of red-green chromatic contrast are sufficiently sensitive to detect visual dysfunction caused by mercury toxicity.

Mercury toxicity in the Amazon: contrast sensitivity and color discrimination of subjects exposed to mercury

We measured visual performance in achromatic and chromatic spatial tasks of mercury-exposed subjects and compared the results with norms obtained from healthy individuals of similar age. Data were obtained for a group of 28 mercury-exposed subjects, comprising 20 Amazonian gold miners, 2 inhabitants of Amazonian riverside communities, and 6 laboratory technicians, who asked for medical care. Statistical norms were generated by testing healthy control subjects divided into three age groups. The performance of a substantial proportion of the mercury-exposed subjects was below the norms in all of these tasks. Eleven of 20 subjects (55 percent) performed below the norms in the achromatic contrast sensitivity task. The mercury-exposed subjects also had lower red-green contrast sensitivity deficits at all tested spatial frequencies (9/11 subjects; 81 percent). Three gold miners and 1 riverine (4/19 subjects, 21 percent) performed worse than normal subjects making more mistakes in the color arrangement test. Five of 10 subjects tested (50 percent), comprising 2 gold miners, 2 technicians, and 1 riverine, performed worse than normal in the color discrimination test, having areas of one or more MacAdam ellipse larger than normal subjects and high color discrimination thresholds at least in one color locus. These data indicate that psychophysical assessment can be used to quantify the degree of visual impairment of mercury-exposed subjects. They also suggest that some spatial tests such as the measurement of red-green chromatic contrast are sufficiently sensitive to detect visual dysfunction caused by mercury toxicity.

A genomic-scale search for regulatory binding sites in the integration host factor regulon of Escherichia coli K12

We examined general aspects of the DNA-protein interaction between the integration host factor (IHF) global regulator and its regulatory binding sites in the Escherichia coli K12 genome. Two models were developed with distinct weight matrices for the regulatory binding sites recognized by IHF. Using these matrices we performed a genome scale scan and built a set of computationally predicted binding sites for each of the models. The sites found by the model associated with repetitive sequences had a higher score in the sequence to matrix alignment. They were also more rare than the other sites. The sites not associated with repeats rapidly tended to become undistinguishable from the background as statistical stringency was relaxed. We compared our results to the known sites documented in RegulonDB and found new members of the IHF Regulon. The two models exhibit clearly distinct affinity patterns (scores in the sequence to matrix alignments and in the number of regulatory sites), as we vary the stringency of the statistical confidence parameters. We suggest that these differences may play an important role in the dynamics of the network. We concluded that IHF may regulate two genes encoding ATP-dependent RNA helicases. This interaction is not described in RegulonDB, even as a computational prediction. IHF may also regulate RNA modification processes.

Mapping cancer, cardiovascular and malaria research in Brazil.

This paper presents performance indicators for the Brazilian cancer, cardiovascular and malaria research areas from 1981 to 1995. The data show an increasing number of papers since 1981 and author numbers indicate a continuous growth of the scientific community and suggest an expected impact of scientific activity on biomedical education. The data also characterize cardiovascular research as a well-established area and cancer research as a faster growing consolidating field. The 1989-1994 share of Brazilian articles among world publications shows a growing trend for the cancer (1.61) and cardiovascular (1.59) areas, and a decrease for the malaria area (0. 89). The burden of the three diseases on society is contrasted by the small number of consolidated Brazilian research groups, and a questionable balance of thematic activity, especially with regard to malaria. Brazilian periodicals play an important role in increasing the international visibility of science produced in the country. Cancer and cardiovascular research is strongly concentrated in the Southeastern and in Southern regions of Brazil, especially in São Paulo (at least one address from São Paulo in 64.5% of the 962 cancer articles and in 66.9% of the 2250 cardiovascular articles, the second state being Rio de Janeiro with at least one address in 14.1 and 11% of those articles, respectively). Malaria research (468 articles) is more evenly distributed across the country, following the pattern of the endemic distribution of the disease. Surveying these national indicator trends can be useful to establish policies in the decision process about health sciences, medical education and public health.

Mapping cancer, cardiovascular and malaria research in Brazil

This paper presents performance indicators for the Brazilian cancer, cardiovascular and malaria research areas from 1981 to 1995. The data show an increasing number of papers since 1981 and author numbers indicate a continuous growth of the scientific community and suggest an expected impact of scientific activity on biomedical education. The data also characterize cardiovascular research as a well-established area and cancer research as a faster growing consolidating field. The 1989-1994 share of Brazilian articles among world publications shows a growing trend for the cancer (1.61) and cardiovascular (1.59) areas, and a decrease for the malaria area (0.89). The burden of the three diseases on society is contrasted by the small number of consolidated Brazilian research groups, and a questionable balance of thematic activity, especially with regard to malaria. Brazilian periodicals play an important role in increasing the international visibility of science produced in the country. Cancer and cardiovascular research is strongly concentrated in the Southeastern and in Southern regions of Brazil, especially in São Paulo (at least one address from São Paulo in 64.5 percent of the 962 cancer articles and in 66.9 percent of the 2250 cardiovascular articles, the second state being Rio de Janeiro with at least one address in 14.1 and 11 percent of those articles, respectively). Malaria research (468 articles) is more evenly distributed across the country, following the pattern of the endemic distribution of the disease. Surveying these national indicator trends can be useful to establish policies in the decision process about health sciences, medical education and public health

Involvement of GABA and ACh in retinal spreading depression: effects of "low calcium-high magnesium" solutions.

Experiments have been performed on isolated chick retinas to demonstrate the participation of gabaergic and cholinergic systems in spreading depression (SD). Gamma-aminobutyric acid (GABA) and acetylcholine (ACh) were measured in the effluent solution of superfused retinas. The influence of changes in the concentration of calcium/magnesium on the release of these neurotransmitters was studied. GABA and ACh are released in the superfusate of retinas during SD. Such release was observed during experimental periods longer than 2 h during which SD was elicited regularly at 15-20 min intervals. Decreasing calcium concentration from 1.0 to 0.5 mM and simultaneously increasing magnesium from 1.0 to 2.0-4.0 mM led to a decrease in GABA and ACh release during SD. Variations in light-scattering and increases in potassium concentration, usually occurring during SD, also decreased when superfusing with low calcium/high magnesium solutions. Lowering calcium concentration to 0.5 mM and increasing magnesium to 2.0 mM eventually turned the tissue refractory to SD. Sometimes a magnesium concentration of 2.0 mM was not effective in blocking SD. However, this blockage could be attained by increasing the concentration of magnesium to 4.0 mM. The effects of low calcium - high magnesium solutions on GABA and ACh release during SD suggests that the release of the substances is at least partially due to synaptic activity. It is not yet possible to establish whether GABA and ACh release is essential for the occurrence of SD. Nevertheless such release suggest that these neurotransmitters could influence the characteristics of SD manifestations in the retina.

Cholinergic neurotransmission in retinal spreading depression.

Experiments performed to demonstrate the participation of cholinergic synapses in retinal spreading depression (SD) have shown that: (1) acetylcholine (ACh) is liberated during SD, its concentration increasing up to 10(-4) mM in the superfusate of one eye cup; (2) the susceptibility of the retina to SD and the velocity of propagation of circling SD are influenced by cholinergic and anticholinergic drugs. ACh 1 mM is effective in eliciting the reaction, whereas d-tubocurarine 0.01 mM and atropine 0.25 mM block this effect. Prostigmine 0.075 mM is able to trigger the reaction and also potentiates the effect of ACh. The velocity of propagation is decreased by ACh 0.25-1.0 mM and prostigmine 0.030 mM, which also potentiate this effect of ACh. Pulses of d-tubocurarine 0.005-0.030 mM and atropine 0.025-0.30 mM decrease the velocity of propagation. However, they block the effect of ACh if they are continuously present in the superfusing solution; (3) the effects of ACh are not blocked by tetrodotoxin 3.19 x 10(-3) mM.