Coordination and Bioorganometallic Chemistry: Exploring the Potential Applications of Metal Coordination and Organometallic Complexes in Medical and Microbiological Advancements.

In the field of coordination and bioorganometallic chemistry, a notable shift is occurring. This mini-review explores a new generation of carefully 3D-crafted coordination and organometallic complexes that differ from conventional structures. Emphasizing disease intervention and microbial control, these compounds, incorporate noble and transition metals, and aim to enhance therapeutic efficacy while minimizing potential health risks. The mini-review covers diverse applications, showcasing their effectiveness against bacteria, viruses, fungi, and as potential tools in cancer treatment. Additionally, it sheds light on the inventive aspects of these complexes within biological systems. By highlighting advancements in bioorganometallic chemistry, the review offers insights and guidance for future developments in safer and more effective therapeutics.

Stability, spectroscopic, electrochemistry and QTAIM analysis of Cu-Znn-1On clusters for glucose sensing application: A study on theoretical and experimental insights.

Clusters of (ZnO)n (n = 2-4) have been shown to play a central role in the detection of glucose entity based on the existence of photo-induced electrons (PE), which facilitates the interaction between (ZnO)n clusters and glucose entity guests. The electrochemistry experiment has confirmed the detection of glucose by the title clusters. The optimization, energetic parameters, and vibrational frequency calculations have indicated that the Cu-Znn-1On-glucose are more stable than the (ZnO)n-glucose complexes. It has been demonstrated that the Cu doping enhanced the chemical behavior of the clusters and formed a high intramolecular charge transfer (ICT) in the system. The glucose sensing by all the forms of Cu-Znn-1On clusters showed that the Cu-Zn3O4, Cu-Wurtzite, and Cu-Rocksalt clusters are the most suitable for adsorbing the glucose guest. The HOMO/LUMO iso-surfaces of the complexes showed that the electron concentrations are localized in the d orbitals and mainly in the form of the d10 orbitals around Zn atoms. The molecular electrostatic potential (MEP) has clearly indicated that a high charge transfer occurs between the copper and the oxygen atoms, which facilitate the adsorption of glucose. The reactivity parameters also indicated that the Wurtzite-glucose complex has a high electrophilicity index (ω), which means a good acceptor behavior to interact with glucose. Additionally, the bond between the (ZnO)n clusters and the glucose polar element has been studied in detail by using QTAIM theory. Finally, the theoretical and experimental studies prove that the Cu-Znn-1On clusters are very suitable and competent compounds for detecting glucose.

Azo-methoxy-calix[4]arene complexes with metal cations for chemical sensor applications: Characterization, QTAIM analyses and dispersion-corrected DFT- computations.

In this work, the structures, quantum chemical descriptors, morphologic characterization of the azo-methoxy-calix[4]arene were investigated. The analyses and interpretation of the theoretical and the experimental IR spectroscopy results for the corresponding compounds was performed. The complexation of the azo-methoxy-calix[4]arene with Zn2+,Hg2+ , Cu2+ , Co2+, Ni2+ , Pb2+ and Cd2+metal cations has been calculated by the dispersion corrected density functional theory (DFT-D3). The values of the interaction energies show that the specific molecule is more selective to the Cu2+ cation. The study of the reactivity parameters confirms that the azo-methoxy-calix[4]arene molecule is more reactive and sensitive to the Cu2+ cation than that Co2+ and Cd2+. In addition, the investigation of the electrophilic and nucleophilic sites has been studied by the molecular electrostatic potential (MEP) analysis. The Hirshfeld surface (HS) analysis of the azo-methoxy-calix[4]arene-Cu2+ interaction have been used to understand the Cu⋯hydrogen-bond donors formed between the cation and the specific compound. The Quantum Theory of Atoms in Molecules (QTAIM) via Non covalent Interaction (NCI) analysis was carried out to demonstrate the nature, the type and the strength of the interaction formed between the Cu2+ cation and the two symmetrical ligands and the cavity. Finally, the chemical sensor properties based on the Si/SiO2/Si3N4/Azo-methoxy-calix[4]arene for detection of Cu2+ cation were studied. Sensing performances are determined with a linear range from 10-5.2 to 10-2.2 M. The Si/SiO2/Si3N4/azo-methoxy-calix[4]arene structure is a promoter to have a good performance sensor.

Nosocomial infections with metallo-beta-lactamase-producing Pseudomonas aeruginosa: molecular epidemiology, risk factors, clinical features and outcomes.

BACKGROUND: Metallo-ß-lactamases (MBLs) have emerged as one of the most important bacterial resistance mechanisms because of their ability to hydrolyse virtually all ß-lactam agents. MBL-producing Pseudomonas aeruginosa (MBL-PA) are an important cause of nosocomial infections, particularly in intensive care units (ICUs), where they are associated with serious infections and present a significant clinical risk. AIM: To assess the molecular epidemiology, risk factors and outcomes of nosocomial infections caused by MBL-PA in a teaching hospital in Southern Brazil. METHODS: From January 2001 to December 2008, 142 carbapenem-resistant P. aeruginosa strains were isolated from distinct clinical samples from hospitalized patients. These isolates were screened for MBLs, and underwent polymerase chain reaction, sequencing and pulsed-field gel electrophoresis (PFGE). Patients infected with carbapenem-resistant MBL-PA were considered as cases, and patients infected with non-MBL-PA were considered as controls. FINDINGS: Eighty-four of 142 patients with positive carbapenem-resistant P. aeruginosa cultures met the criteria of the Centers for Disease Control and Prevention for infection. Fifty-eight patients were infected with MBL-PA (69%) and 26 patients were infected with non-MBL-PA (31%). Multi-variate analysis revealed that ICU stay [P = 0.003, odds ratio (OR) 4.01, 95% confidence interval (CI) 1.15-14.01] and urinary tract infection (P = 0.001, OR 9.67, 95% CI 1.72-54.48) were important risk factors for MBL-PA infection. Patients infected with MBL-PA showed faster onset of infection (P = 0.002) and faster progression to death (P = 0.04). CONCLUSIONS: These results showed the severity of MBL-PA infections, and demonstrated the urgent need for strategies to improve infection control measures to prevent an increase in these nosocomial infections.

Stem cells and androgen receptor in human periapical periodontitis / Células madre y receptor de andrógenos en periodontitis periapical humana

Activation of macrophages in periapical granulomas occurs through the presence of cytokines, endotoxin and other genetic and epigenetic factors, allowing the initiation of inflammation and bone resorption. The present study aims to analyze the presence of CD133 protein (marker of stem cells) and the AR (androgen receptor) protein in biopsies of human odontogenic periapical granuloma. Biopsies from 14 adult male patients with diagnosis of periapical granuloma included in paraffin blocks were processed histologically to obtain 5-um thick sections. Protein presence was detected and analyzed by immunohistochemistry of CD133 and AR. The quantification considered the number of positive cells in 0.17 mm2 random areas under the microscope using a 1000X objective. Both CD133 and AR proteins are expressed abundantly in cells in pathological periapical granulomas tissue. The number of cells expressing CD133 and AR shows a wide variation coefficient, so its variation is a particular feature for each individual. We concluded that in human odontogenic periapical granuloma there are abundant stem cells and cells expressing AR that may be important for the pathogenic inflammatory process.

La activación de los macrófagos en los granulomas periapicales humanos se producen a través de la presencia de citoquinas, endotoxinas y otros factores genéticos y epigenéticos que permiten la iniciación de la inflamación y la reabsorción ósea. El presente estudio pretende analizar la presencia de proteína CD133 (marcador de células madre) y de la proteína RA (receptor de andrógenos) en las biopsias de granulomas periapicales odontogénicos humanos. Las biopsias de 14 pacientes varones adultos con diagnóstico de granuloma periapical fueron incluidos en bloques de parafina y se procesaron histológicamente para obtener secciones de 5 micras de espesor. La presencia de CD133 y RA fueron detectadas y analizadas por inmunohistoquímica. La cuantificación se realizó considerando el número de células positivas en áreas al azar de 0,17mm2, utilizando microscopio con objetivo de 1000X. Ambas proteínas, CD133 y RA se expresan en abundancia en las células del tejido patológico con granuloma periapical. El número de células que expresan CD133 y RA presentan un amplio coeficiente de variación, por lo que su variación es una característica particular de cada individuo. Se concluye que en granuloma periapical odontogénico humano se expresan abundantes células madre y proteínas receptoras de andrógenos, antecedentes que pueden sermuy importantes en la expresión y diagnosis de los procesos patológicos inflamatorios.

Histological description of the interaction between muscle fibers and connective tissue of the fascia of the human trapezius muscle / Descripción histológica de la interacción entre las fibras musculares y tejido conectivo de la fascia del músculo trapecio humano

The skeletal muscle fascia corresponds to a condensation of connective tissue. Fascias are highly innervated and sensitive, and can cover non-expandable structures as well as musculature. It is suggested that fascias have a pivotal role in functions such as postural regulation, peripheral motor coordination and proprioception. Also, the presence of inflammation and microcalcification in fascia of patients with localized muscle pain has been described, suggesting a pathogenic role in pain. The aim was to describe the histological structure of the external deep fascia of the trapezius muscle, with emphasis on the content and arrangement of muscle fibers, type I collagen, and adipose tissue. Sample material was obtained from a male cadaver (60-70 years old), by dissection of the posterior cervical region of the superficial fascia of the trapezius muscle and fixed in buffered formalin. Samples were processed by routine histological techniques and embedded in paraffin, obtaining 5 µm-thick sections that were stained according to the van Gieson technique. The trapezius fascia is composed of type I collagen, organized into high-density collagen bundles and oriented in different directions, and by adipocytes disposed in longitudinal groups on the main axis of the fascia. Muscle fibers are organized into bundles that are inserted laterally on the thickness of the fascia. It is possible that lateral transmission of tensional forces between the fibers might be present.

La fascia del músculo esquelético corresponde a una condensación de tejido conectivo. Las fascias están inervadas y son sensibles y pueden cubrir estructuras no distensibles, así como las fibras musculares esqueléticas. Tienen un rol importante en la regulación de la postura, la coordinación motora periférica y la propiocepción. Además, se ha descrito la presencia de inflamación y microcalcificaciones en la fascia de los pacientes con dolor muscular localizado, lo que sugiere un rol patogénico en el dolor. El objetivo del trabajo fue describir la estructura histológica de la fascia externa profunda del músculo trapecio, con énfasis en el contenido y la disposición de las fibras musculares, colágeno tipo I y el tejido adiposo. Material y métodos: El material de la muestra fue obtenido de un cadáver de sexo masculino (60-70 años), por la disección de la región cervical posterior de la fascia superficial del músculo trapecio e inmediatamente fijado en formalina tamponada (pH 7,2) durante 48 horas. La muestra fue procesada por técnicas histológicas e impregnada en parafina (punto de fusión 56-58 C). Secciones de 5 µm de espesor fueron montadas en láminas silanizada para el desarrollo del protocolo de la técnica de van Gieson. Resultados y discusión: Se observa que la fascia del trapecio está compuesta por tejido conectivo denso irregular con abundante colágeno tipo I, organizado en paquetes grandes como verdaderos haces de colágeno de alta densidad orientada en diferentes direcciones; y por adipocitos dispuestos en grupos longitudinales en el eje principal de la fascia. Las fibras musculares estriadas están organizadas en paquetes que se insertan lateralmente en el espesor de la fascia. Es posible que la transmisión lateral de la tensión entre las fibras esté presente.

Molecular analysis of a mutant Anticarsia gemmatalis multiple nucleopolyhedrovirus (AgMNPV) shows an interruption of an inhibitor of apoptosis gene (iap-3) by a new class-II piggyBac-related insect transposon.

A new piggyBac-related transposable element (TE) was found in the genome of a mutant Anticarsia gemmatalis multiple nucleopolyhedrovirus interrupting an inhibitor of apoptosis gene. This mutant virus induces apoptosis upon infection of an Anticarsia gemmatalis cell line, but not in a Trichoplusia ni cell line. The sequence of the new TE (which was named IDT for iap disruptor transposon) has 2531 bp with two DNA sequences flanking a putative Transposase (Tpase) ORF of 1719 bp coding for a protein with 572 amino acids. These structural features are similar to the piggyBac TE, also reported for the first time in the genome of a baculovirus. We have also isolated variants of this new TE from different lepidopteran insect cells and compared their Tpase sequences.

Efeitos da crioterapia, estimulação elétrica transcutânea e da sua associação na atividade elétrica do nervo femoral em ratos / Effects of cryotherapy, transcutaneous electrical stimulation and their combination on femoral nerve electrical activity in rats

CONTEXTUALIZAÇÃO: Relatos clínicos sugerem que a associação terapêutica entre crioterapia (CRIO) e estimulação elétrica transcutânea (TENS) favorece analgesia local. OBJETIVO: Avaliar a atividade elétrica do nervo femoral (ANF), em repouso e durante a aplicação isolada, e associada de TENS e CRIO em ratos. MÉTODOS: Foram utilizados nove ratos (Wistar) adultos com peso de ±300g. Após anestesia (Uretana, 1mg/g i.p.), o nervo femoral direito foi isolado para registro da ANF basal e durante as modalidades analgésicas. Depois da fixação dos eletrodos no terço inferior da coxa direita, foram aplicadas TENS (50Hz, 10mÅ) por cinco minutos, CRIO isolada e terapia associada (TA) por dez minutos. Os registros contínuos da ANF foram realizados por meio de um amplificador de potenciais de ação, avaliados posteriormente no primeiro, quinto e décimo minuto em unidades arbitrárias (Ua). Utilizaram-se a análise de variância (ANOVA) uma via e o teste de Dunnett como post-hoc. Valores expressos como média ±EPM e as diferenças fixadas em p<0,05. RESULTADOS: A atividade do nervo femoral aumentou (p<0,01) na TENS (0,358±0,09Ua) e na TA (0,230±0,07Ua) e ficou inalterada após CRIO (0,063±0,003Ua), em relação ao basal inicial (0,009±0,0003Ua). No quinto minuto, observou-se uma significante (p<0,05) atenuação da ANF na modalidade TA (0,144±0,027Ua) versus TENS isolada (0,324±0,089Ua). CONCLUSÕES: A associação entre as modalidades analgésicas não-invasivas CRIO e TENS atenua significativamente os efeitos produzidos pela TENS isoladamente sobre a ANF de ratos anestesiados.

BACKGROUND: Clinical reports suggest that the therapeutic association between cryotherapy (CRYO) and transcutaneous electrical stimulation (TENS) favors local analgesia. OBJECTIVE: To evaluate the electrical activity of the femoral nerve (FNA), at rest and during single and combined application of TENS and CRYO, in rats. METHODS: Nine adult Wistar rats weighting ±300g were used in this study. After inducing anesthesia (Urethane, 1mg/g i.p.), the right femoral nerve was isolated in order to record the FNA at baseline and during the therapeutic modalities. After attaching the electrodes to the lower third of the right thigh, TENS (50Hz, 10mÅ) was applied for five minutes, and CRYO and the combined therapy (CT) for ten minutes. The FNA was recorded continuously by means of an action potential amplifier and the recordings from the first, fifth and tenth minutes were subsequently evaluated using arbitrary units (aU). One-way analysis of variance (ANOVA) was used, with Dunnett's test as post-hoc analysis. The values were expressed as the mean ±SEM and differences were established at p<0.05. RESULTS: The femoral nerve activity increased (p<0.01) after TENS (0.358±0.09aU) and CT (0.230±0.07aU) and was unchanged after CRYO (0.063±0.003aU), in relation to the baseline (0.009±0.0003aU). In the fifth minute, we observed significant (p<0.05) attenuation of FNA in the CT (0.144±0.027aU) in relation to TENS alone (0.324±0.089aU). CONCLUSIONS: The association between CRYO and TENS noninvasive analgesia significantly attenuates the effects produced by TENS alone on the FNA of anesthetized rats.

Cellular senescence bypass screen identifies new putative tumor suppressor genes.

Senescence is a mechanism that limits cellular lifespan and constitutes a barrier against cellular immortalization. To identify new senescence regulatory genes that might play a role in tumorigenesis, we have designed and performed a large-scale antisense-based genetic screen in primary mouse embryo fibroblasts (MEFs). Out of this screen, we have identified five different genes through which loss of function partially bypasses senescence. These genes belong to very different biochemical families: csn2 (component of the Cop9 signalosome), aldose reductase (a metabolic enzyme) and brf1 (subunit of the RNA polymerase II complex), S-adenosyl homocysteine hydrolase and Bub1. Inactivation, at least partial, of these genes confers resistance to both p53- and p16INK4a-induced proliferation arrest. Furthermore, such inactivation inhibits p53 but not E2F1 transcriptional activity and impairs DNA-damage-induced transcription of p21. Since the aim of the screen was to identify new regulators of tumorigenesis, we have tested their inactivation in human tumors. We have found, either by northern blot or quantitative reverse transcriptase-PCR analysis, that the expression of three genes, Csn2, Aldose reductase and Brf1, is lost at different ratios in tumors of different origins. These genes are located at common positions of loss of heterogeneity (15q21.2, 7q35 and 14q32.33); therefore,we have measured genomic losses of these specific genes in different tumors. We have found that Csn2 and Brf1 also show genomic losses of one allele in different tumors. Our data suggest that the three genes identified in the genome-wide loss-of-function genetic screen are putative tumor suppressors located at 15q21.2; 7q35 and 14q32.33.

Large scale genetic screen identifies MAP17 as protein bypassing TNF-induced growth arrest.

Although activated macrophages destroy cancer cells more effectively than normal cells, the ability to escape activated macrophages is a characteristic of tumor cells. One of the mechanisms responsible for the specific killing of tumor cells by macrophages is the production of the cytokine tumor necrosis factor (TNF) alpha. Therefore, resistance to TNF may provide such cancer cells a selective advantage against host elimination. With the aim of identifying genes with these properties we undertook a large scale genetic screen to identify genes able to bypass TNF-induced G1 arrest. We identified MAP17, a small 17 kDa nonglycosylated membrane protein that localizes to the plasma membrane and the Golgi apparatus. Ectopic expression of MAP17 in tumor cells prevents TNF-induced G1 arrest by impairing p21waf1 induction. However, expression of MAP17 does not inhibit TNF-induced apoptosis in Me180-sensitive tumor cells. The inhibition of TNF is specific since MAP17 does not alter the response to other cytokines such as IFNgamma. As described in the Xenopus oocyte system, MAP17 increases the uptake of mannose in some cells, but this effect is not responsible for TNF bypass. We have also analyzed the expression of MAP17 mRNA in a panel of cell lines. MAP17 is expressed in 30% of cell lines of different origin. However, MAP17 mRNA expression did not correlate with TNF resistance. Our data indicates that although MAP17 expression might bypass TNF-induced growth arrest, it is not the only determinant of this response.

The inhibitor of apoptosis gene (iap-3) of Anticarsia gemmatalis multicapsid nucleopolyhedrovirus (AgMNPV) encodes a functional IAP.

Programmed cell death or apoptosis is one of the defense mechanisms used by insect cells in response to baculovirus infection. Baculoviruses harbour antiapoptotic genes to prevent apoptosis and to maintain the normal course of infection. In this work, we showed that, like other baculoviruses, Anticarsia gemmatalis multicapsid nucleopolyhedrovirus (AgMNPV) has a functional inhibitor of apoptosis gene (iap-3). The iap-3 gene was cloned, sequenced and its transcription confirmed by RT-PCR. The putative iap-3 gene of the baculovirus AgMNPV has 864 nucleotides and codes an ORF of 287 amino acids. We have found two BIR motifs (baculoviral iap repeats) at the amino-terminal region and a carboxi-terminal RING finger motif. The IAP-3 protein of AgMNPV is closely related to IAP-3 proteins of baculoviruses and lepidopteran IAPs, with most amino acid identity (75%) with the IAP-3 protein of CfDefNPV (Choristoneura fumiferana DEF nucleopolyhedrovirus). Transcriptional analysis of the AgMNPV iap-3 gene showed that iap-3-specific transcripts could be detected early and late in the infection. The iap-3 gene of AgMNPV was shown to encode a functional IAP since insect cells transfected with increasing amounts of a plasmid containing the iap-3 of AgMNPV showed increased resistance to apoptosis induced by a AgMNPV mutant virus.

Changes in monoaminergic activity in the anterior, medium and posterior hypothalamus, gonadotropins levels and ovarian hormones during puberty of the female rat.

The aim of present study is the analysis of monoamines concentrations changes in the anterior, medium and posterior hypothalamus, as well as changes in serum gonadotropins levels, ovarian steroids and follicular growth during the prepubertal development of the female rat. Noradrenergic activity in the anterior, medium and posterior hypothalamus reached highest level at day 13 after birth, followed by a subsequent decrease from day 15 to 19 and an increase on days 22 and 27 postnatal. At day 1, neural activity in the medium hypothalamus was higher than the activity in the anterior and posterior hypothalamus. Serotoninergic activity in three portions of the hypothalamus was higher throughout the prepubertal development. Follicle-stimulating hormone and luteinizing hormone serum levels increased between days 11 and 17 and decreased from day 19 to 36. The concentration of 17beta-estradiol was consistently low throughout the prepubertal development and increased at day 39 after birth. These results indicate that during the prepubertal development of the rat, the three regions of the hypothalamus show significant changes in the monoaminergic neural activity. There is an inverse relationship between the noradrenergic activity on the anterior and medium hypothalamus and serotoninergic activity in the posterior hypothalamus with ovarian steroids during sexual maturation. These changes may be linked to the development of the neuroendocrine processes that modulate gonadotropin secretion and ovarian function.

Influence of thyroid hormone on 5-HT(1A) and 5-HT(2A) receptor-mediated regulation of hippocampal BDNF mRNA expression.

The aim of the present study was to determine the influence of thyroid hormone, T3, on the regulation of hippocampal BDNF expression by 5-HT receptor agonists. Chronic T3 administration prior to treatment with the 5-HT(1A) agonist, 8-OH-DPAT, significantly decreased BDNF mRNA in the dentate gyrus region of the hippocampus. Administration of 8-OH-DPAT did not alter hippocampal BDNF mRNA expression in naive, euthyroid rats. Pretreatment with the 5-HT(1A) antagonist, WAY 100635, completely blocked the 8-OH-DPAT-induced down-regulation of BDNF mRNA in chronic T3-treated rats. Acute T3 administration prior to 8-OH-DPAT treatment led to a small, but significant, decrease in hippocampal dentate gyrus BDNF mRNA. Acute or chronic administration of T3 did not alter the decrease in hippocampal BDNF mRNA induced by the 5-HT(2A/2C) receptor agonist, DOI. The influence of 8-OH-DPAT and DOI on hippocampal BDNF mRNA was also unaltered in rats rendered hypothyroid by propylthiouracil administration. Chronic T3 treatment or hypothyroidism did not influence the basal expression of hippocampal BDNF mRNA. The affinity and density of 5-HT(1A) receptors, and the hippocampal expression of 5-HT(1A) mRNA were also not influenced by chronic T3 treatment. The results of this study clearly demonstrate a powerful interaction between thyroid hormone and the 5-HT(1A) receptor in the regulation of hippocampal BDNF expression. Crosstalk between signal transduction cascades influenced by T3 and 5-HT(1A) receptors may mediate the synergistic effects of these systems on hippocampal BDNF expression.

Production of viral progeny in insect cells undergoing apoptosis induced by a mutant Anticarsia gemmatalis nucleopolyhedrovirus.

The Anticarsia gemmatalis nucleopolyhedrovirus (AgMNPV) is the most successful viral biopesticide in use worldwide. We have demonstrated that despite widespread apoptosis and no protein synthesis at 48 h p.i., UFL-AG-286 cells infected with a mutant of AgMNPV (vApAg), produced significant amounts of budded virus (BVs) and viral DNA late in infection. However, a different susceptible cell line (BTI-Tn5B 1-4) showed no signs of apoptosis and produced 3.5 times more budded virus when infected with vApAg. A comparison of DNA from AgMNPV and vApAg digested with the same restriction enzymes showed differences in the restriction pattern, indicating that the vApAg phenotype might be due to a mutation in a gene or genes responsible for directly or indirectly inhibiting apoptosis in UFL-AG-286 cells.

beta-blocker binding to human 5-HT(1A) receptors in vivo and in vitro: implications for antidepressant therapy.

A novel strategy for improving the treatment of depressive illness is augmentation of antidepressants with a 5-HT1(1A) autoreceptor antagonist. However, trials using the 5-HT1(1A)/beta-blocker pindolol are proving inconsistent. We report how positron emission tomography (PET) and in vitro autoradiography can inform trials of antidepressant augmentation. We show that in healthy volunteers, in vivo, pindolol (n = 10) and penbutolol (n = 4), but not tertatolol (n = 4) occupy the human 5-HT(1A) receptors, at clinical doses. Pindolol, as well as the beta-blockers penbutolol and tertatolol, has high affinity for human 5-HT(1A) receptors in post-mortem brain slices (n = 4). Pindolol shows preference for 5-HT(1A) autoreceptors versus the post-synaptic receptors both in vitro and in vivo. Our data reveal that pindolol doses used in antidepressant trials so far are suboptimal for significant occupancy at the 5-HT(1A) autoreceptor. Penbutolol or higher doses of pindolol are candidates for testing as antidepressant augmenting regimes in future clinical trials.

Dípteros muscóides de importância média e veterinária e seus parasitóides em Goiás / Muscoid dipterous of medical and veterinary importance and their parasitoids in Goias State, Brazil

The objective of this work was to identify flies of medical and veterinary importance and their natural enemies, located around the city of Itumbiara, GO, Brazil. Five thousand eight hundred and twenty-five muscoid dipterous insects and parasitoids were collected from a Brazilian savanna (cerrado) area of Itumbiara. Substrates for obtaining flies were liver. The most frequent fly and parasitoid species found were: Fannnia pusio (29.2 per cent) and Atherigona orientalis (26.8 per cent) (flies), Nasonia vitripennis (56.0 per cent) and Brachymeria sp. (26.6 per cent) (parasitoids). Musca domestica was the dipterous species of greatest sanitary importance collected. This is the first report of the species Brachymeria sp. and Hememcyrtus sp. in the State of Goias. Data contribute to the knowledge of dipterous and parasitoids fauna in the state of Goias

Affinity of (+/-)-pindolol, (-)-penbutolol, and (-)-tertatolol for pre- and postsynaptic serotonin 5-HT(1A) receptors in human and rat brain.

There is considerable interest in the use of drugs that selectively block presynaptic (somatodendritic) serotonin 5-HT(1A) receptors for the adjunctive treatment of major depressive disorder. The 5-HT(1A)/beta-adrenoceptor ligands (+/-)-pindolol, (-)-tertatolol, and (-)-penbutolol are currently under clinical investigation, and knowledge of their affinity at different populations of central 5-HT(1A) receptors is needed. Here we have determined the affinity of these drugs for presynaptic and postsynaptic 5-HT(1A) receptors in postmortem human and rat brain using receptor autoradiography and the selective 5-HT(1A) radioligand [(3)H]WAY-100635. The binding of [(3)H]WAY-100635 was specific and saturable and showed high affinity in the rat dorsal raphe nucleus and hippocampus (K(D) = 1.5-1.7 nM). In competition studies, the three compounds had nanomolar affinity and produced monophasic displacement of [(3)H]WAY-100635 binding in all regions of both species. (-)-Penbutolol and (-)-tertatolol had similar affinity for pre-and postsynaptic 5-HT(1A) receptors in both rat and human brain. However, in the human, but not the rat, the affinity of (+/-)-pindolol in dorsal raphe nucleus (K(i) = 8.9 +/- 1. 1 nM) was slightly but significantly higher than that in hippocampus (K(i) = 14.4 +/- 1.5 nM in CA1). In summary, our data show that (+/-)-pindolol, (-)-tertatolol, and (-)-penbutolol are all high-affinity ligands at native human and rat 5-HT(1A) receptors. (-)-Penbutolol and (-)-tertatolol do not discriminate between the pre- and postsynaptic 5-HT(1A) sites tested in either species, but (+/-)-pindolol showed a slightly higher affinity for the presynaptic site in human brain. Further work is needed to establish whether the latter difference is clinically relevant.

Host-specific transcription of nucleopolyhedrovirus gene homologues in productive and abortive Anticarsia gemmatalis MNPV infections.

In a previous report, we showed that Anticarsia gemmatalis nucleopolyhedrovirus (AgMNPV) infections of Choristoneura fumiferana IPRI-CF-124T and Bombyx mori BM-5 cell lines are abortive, whereas A. gemmatalis UFL-AG-286 cells efficiently produce infectious virus and polyhedral inclusion bodies (PIBs). In the present study, we explored transcription patterns in these infections using representative temporal classes of Autographa californica MNPV (AcMNPV) genes. Northern analyses were carried out using internal fragments of AcMNPV genes that hybridized strongly with AgMNPV genomic DNA. The results showed that ie-1 (immediate-early) homologue, but not dnapol (delayed-early) homologue of AgMNPV was transcribed efficiently in the abortive infections. Transcription of gp67 (late) and polh (very late) homologues was minimal in C. fumiferana cells and undetectable in B. mori cells. Transcription patterns in AgMNPV-infected A. gemmatalis cells were similar to those reported for productive AcMNPV infections. These data are consistent with our previous observation that early cytopathic effect, but not infectious virus or PIBs are detected in abortive infections with AgMNPV. Our results suggest that C. fumiferana and B. mori cells restrict AgMNPV infections at the transcriptional level and that this block likely occurs between immediate-early and delayed-early phases of the NPV cycle. Our data do not preclude the possibility of additional restrictions at other stages.

Effects of a lesion in the dorsal raphe nuclei performed during the juvenile period of the female rat, on puberty.

The present study examined the effect of thermic lesions on the dorsal raphe nuclei (DRN) of the female rat, performed at various ages during the prepubertal period (21, 24, or 27 days), on puberty, and at first ovulation. In comparison with sham-operated animals, the age of vaginal opening and first vaginal oestrus was delayed in rats with a DRN lesion performed at the end of the infantile period (day 21) (45.6+/-0.94 vs. 89.9+/-1.03, p < 0.05), whereas differences were not observed in animals with lesions performed during the juvenile period (day 24 or 27). The number of ova shed by ovulating animals was greater in those rats with lesions performed on day 24 or 27 (9.7+/-0.4 vs. 7.4+/-0.4; 9.5+/-0.5 vs. 7.7+/-0.4, p < 0.05). Ovarian follicular atresia in these animals was significantly lower than in control and sham-operated ones. On the day of first vaginal oestrus and 48 h after the lesion, the serotonin-hypothalamic concentration decreased in all lesioned animals. Present results support the idea of the participation of the serotoninergic system, arising from the DRN, in the neuroendocrine mechanisms regulating the onset of puberty and the first ovulation, with variations depending on animal maturity.

Oral aluminum administration to rats wih normal renal function. 1. Impairment of erythropoiesis.

Aluminum (Al) toxicity has been mainly investigated in uremic patients although healthy subjects and patients without renal insufficiency are not exempt from its potential deleterious effects. This experimental study aims to elucidate the action of different doses of Al citrate on in vivo erythropoiesis and find out whether the metal exerts a local toxic effect upon the bone marrow late erythroid progenitor cells. The groups in the first experimental series were: C1 (n=5) controls and TAl-1 (n=5) rats receiving 1 micromol Al citrate/g body weight/day by gavage. Colony-forming units-erythroid (CFU-E) development was inhibited in the TAl-1 group, but the median osmotic fragility (MOF) and hematocrit (Ht) values were similar to those of the C1 group. The groups in the second series were C2 (n=5) controls and TAl-2 (n=5) rats receiving Al citrate in drinking water (100 mmol/l). The TAl-2 group showed decreased Ht, hemoglobin concentration, MOF and red blood-cell life-span values (P<0.05), and a marked inhibition of the CFU-E development (P<0.01). Serum and bone Al concentrations were increased in both Al-treated groups (P < 0.01). There was a dose-dependent increase in bone Al levels (P < 0.01) and a dose-dependent decrease of CFU-E development (P<0.05). The CFU-E development was inversely correlated with the bone Al content (r=-0.79; P<0.05). The results demonstrate that even very low doses of Al citrate impair erythropoiesis in vivo and higher doses exert a deleterious action on both CFU-E and mature erythrocytes. This might show a local effect of Al on CFU-E caused by the bone sensitivity to the metal accumulation.