Obesity, diabetes and risk of bone fragility: How BMAT behavior is affected by metabolic disturbances and its influence on bone health.

PURPOSE: Osteoporosis is a metabolic bone disease characterized by decreased bone strength and mass, which predisposes patients to fractures and is associated with high morbidity and mortality. Like osteoporosis, obesity and diabetes are systemic metabolic diseases associated with modifiable risk factors and lifestyle, and their prevalence is increasing. They are related to decreased quality of life, functional loss and increased mortality, generating high costs for health systems and representing a worldwide public health problem. Growing evidence reinforces the role of bone marrow adipose tissue (BMAT) as an influential factor in the bone microenvironment and systemic metabolism. Given the impact of obesity and diabetes on metabolism and their possible effect on the bone microenvironment, changes in BMAT behavior may explain the risk of developing osteoporosis in the presence of these comorbidities. METHODS: This study reviewed the scientific literature on the behavior of BMAT in pathological metabolic conditions, such as obesity and diabetes, and its potential involvement in the pathogenesis of bone fragility. RESULTS: Published data strongly suggest a relationship between increased BMAT adiposity and the risk of bone fragility in the context of obesity and diabetes. CONCLUSION: By secreting a broad range of factors, BMAT modulates the bone microenvironment and metabolism, ultimately affecting skeletal health. A better understanding of the relationship between BMAT expansion and metabolic disturbances observed in diabetic and obese patients will help to identify regulatory pathways and new targets for the treatment of bone-related diseases, with BMAT as a potential therapeutic target.

Melatonin attenuates antipsychotic metabolic effects: an eight-week randomized, double-blind, parallel-group, placebo-controlled clinical trial.

OBJECTIVE: Second-generation antipsychotics (SGAs) are among the first-line treatments for bipolar disorder and schizophrenia, but have a tendency to generate metabolic disturbances. These features resemble a metabolic syndrome for which a central autonomic imbalance has been proposed that may originate from the hypothalamic suprachiasmatic nuclei. In a clinical trial, we hypothesized that melatonin, a hormone that regulates the suprachiasmatic nucleus, could attenuate SGA-induced adverse metabolic effects. METHODS: In an eight-week, double-blind, randomized, placebo-controlled, parallel-group clinical trial, we evaluated the metabolic effect of melatonin in SGA-treated patients in terms of weight, blood pressure, lipid, glucose, body composition, and anthropometric measures. A total of 44 patients treated with SGAs, 20 with bipolar disorder and 24 with schizophrenia, randomly received placebo (n = 24) or melatonin 5 mg (n = 20). RESULTS: The melatonin group showed a decrease in diastolic blood pressure (5.1 versus 1.1 mmHg for placebo, p = 0.003) and attenuated weight gain (1.5 versus 2.2 kg for placebo, F = 4.512, p = 0.040) compared to the placebo group. The strong beneficial metabolic effects of melatonin in comparison to placebo on fat mass (0.2 versus 2.7 kg, respectively, p = 0.032) and diastolic blood pressure (5.7 versus 5.5 mmHg, respectively, p = 0.001) were observed in the bipolar disorder and not in the schizophrenia group. No adverse events were reported. CONCLUSIONS: Our results show that melatonin is effective in attenuating SGAs' adverse metabolic effects, particularly in bipolar disorder. The clinical findings allow us to propose that SGAs may disturb a centrally mediated metabolic balance that causes adverse metabolic effects and that nightly administration of melatonin helps to restore. Melatonin could become a safe and cost-effective therapeutic option to attenuate or prevent SGA metabolic effects.

Helminth infection alters mood and short-term memory as well as levels of neurotransmitters and cytokines in the mouse hippocampus.

UNLABELLED: Helminthic infections are important causes of morbidity and mortality in many developing countries, where children bear the greatest health burden. The ability of parasites to cause behavioral changes in the host has been observed in a variety of host-parasite systems, including the Taenia crassiceps-mouse model. In murine cysticercosis, mice exhibit a disruption in the sexual, aggressive and avoidance predator behaviors. OBJECTIVE: The present study was conducted to characterize short-term memory and depression-like behavior, as well as levels of neurotransmitters and cytokines in the hippocampus of cysticercotic male and female mice. METHODS: Cytokines were detected by RT-PCR and neurotransmitters were quantified by HPLC. RESULTS: Chronic cysticercosis infection induced a decrease in short-term memory in both male and female mice, having a more pronounced effect in females. Infected females showed a significant increase in forced swimming tests with a decrease in immobility. In contrast, male mice showed an increment in total activity and ambulation tests. Serotonin levels decreased by 30% in the hippocampus of infected females whereas noradrenaline levels significantly increased in infected males. The hippocampal expression of IL-4 increased in infected female mice, but decreased in infected male mice. CONCLUSION: Our study suggests that intraperitoneal chronic infection with cysticerci in mice leads to persistent deficits in tasks dependent on the animal's hippocampal function. Our findings are a first approach to elucidating the role of the neuroimmune network in controlling short-term memory and mood in T. crassiceps-infected mice.

Gonadal hormone levels and platelet tryptophan and serotonin concentrations in perimenopausal women with or without depressive symptoms.

INTRODUCTION: The etiology of depressive symptoms associated with the transition to menopause is still unknown; hormonal changes, serotonergic system or insomnia, could be a trigger to depressive symptomatology. The aim of the present study was to evaluate gonadal hormonal levels, platelet serotonin concentrations and platelet tryptophan concentrations in a group of depressed perimenopausal women and their healthy counterparts. METHODS: A total of 63 perimenopausal women between 45 and 55 years old were evaluated; of these, 44 were depressed patients, and 19 were perimenopausal women without depression. The instruments that were applied included the Center for Epidemiologic Studies Depression Scale (CES-D), the Hamilton Depression Rating Scale (HDRS) and the Green Climacteric Scale (GCS); gonadal hormone levels and platelet tryptophan and serotonin concentrations were measured in all participants. Differences in hormonal levels and tryptophan and serotonin concentrations were evaluated with respect to specific symptoms, such as insomnia, hot flashes, nervousness, depressed mood and loss of interest. RESULTS: No differences between groups were observed with respect to hormonal levels and tryptophan and serotonin concentrations; mean sleep hours and insomnia were significantly correlated with platelet tryptophan concentrations. CONCLUSIONS: In this sample, all symptoms of depression could not be explained by platelet tryptophan and serotonin concentrations and hormonal levels; differences were observed only when we evaluated insomnia and hot flashes.

Research Protocol for an Observational Health Data Analysis on the Adverse Events of Systemic Treatment in Patients with Metastatic Hormone-sensitive Prostate Cancer: Big Data Analytics Using the PIONEER Platform.

Combination therapies in metastatic hormone-sensitive prostate cancer (mHSPC), which include the addition of an androgen receptor signaling inhibitor and/or docetaxel to androgen deprivation therapy, have been a game changer in the management of this disease stage. However, these therapies come with their fair share of toxicities and side effects. The goal of this observational study is to report drug-related adverse events (AEs), which are correlated with systemic combination therapies for mHSPC. Determining the optimal treatment option requires large cohorts to estimate the tolerability and AEs of these combination therapies in "real-life" patients with mHSPC, as provided in this study. We use a network of databases that includes population-based registries, electronic health records, and insurance claims, containing the overall target population and subgroups of patients defined by unique certain characteristics, demographics, and comorbidities, to compute the incidence of common AEs associated with systemic therapies in the setting of mHSPC. These data sources are standardised using the Observational Medical Outcomes Partnership Common Data Model. We perform the descriptive statistics as well as calculate the AE incidence rate separately for each treatment group, stratified by age groups and index year. The time until the first event is estimated using the Kaplan-Meier method within each age group. In the case of episodic events, the anticipated mean cumulative counts of events are calculated. Our study will allow clinicians to tailor optimal therapies for mHSPC patients, and they will serve as a basis for comparative method studies.

Anxiolytic-like and antinociceptive effects of 2(S)-neoponcirin in mice.

STUDY AIMS: 2(S)-neopincirin (NEO) is a constituent from of Clinopodium mexicanum, which is used in traditional Mexican herbal medicine for its tranquilizing and analgesic properties. This study investigated the anxiolytic-like, sedative and antinociceptive effects of NEO in several mice models. MATERIAL AND METHODS: The anxiolytic-like effect was evaluated in the hole-board (HBT) and Open Field Tests (OFT); sedative effect was evaluated in sleeping time induced by sodium pentobarbital, and its antinociceptive actions were measured in the hot plate test. To evaluate if the GABA receptor could be involved in the anxiolytic-like effect produced by NEO, in independent experiments, the effects produced by co-administration of NEO plus muscimol (MUS) and NEO plus Pitrotoxin (PTX) were evaluated in the HBT. RESULTS: NEO was isolated from Clinopodium mexicanum leaves. The NMR, MS and optic rotation data helped establish its identity as (2S)-5-hydroxy-4'-methoxyflavanone-7-O-{ß-glucopyranosyl-(1→6)-ß-rhamnoside}. NEO showed an anxiolytic-like effect and was able to counter the nociception induced by a thermal stimulus in a dose-dependent manner. PTX blocked the anxiolytic-like effect of NEO, while MUS was able to enhance it. CONCLUSIONS: The findings of present work demonstrated that NEO possesses anxiolytic-like and antinociceptive effects in mice. Such effects are not associated with changes in the locomotor activity. These results supported the notion that anxiolytic-like effect of NEO involves the participation of GABAergic system.

Physiological Stress Responses in Cattle Used in the Spanish Rodeo.

Certain events can cause distress in cattle. In Spain, there is a sport similar to rodeo called persecution and takedown, in which calves are harassed and knocked down by riders. In this study, the physiological stress response of calves (n = 260) is assessed by measuring hormonal physiological parameters. Salivary samples were collected from Salers (n = 110) and Lidia (n = 150) calves before, during, and after the persecution and takedown event. The hormones epinephrine, cortisol, serotonin, and dopamine were determined in saliva samples using enzyme-immunoassay techniques. The results obtained revealed that epinephrine and cortisol levels increased during the event in Salers calves, with a significant increase (p < 0.05) in the case of epinephrine, although after the event, these values returned to their initial state. Therefore, this sport supposes an assumable punctual stressor stimulus for the animal. In contrast, in Lidia calves, cortisol and epinephrine levels decreased, with a significant decrease (p < 0.05) in the case of cortisol, which may be related to the temperament of this breed and facing a stressful situation in a different manner. This is confirmed by serotonin and dopamine levels that were altered in Lidia calves with respect to the other group studied. In conclusion, the sport of persecution and takedown produces a physiological response of adaptive stress assumable for the animals.

High rate of de novo esophagitis 5 years after sleeve gastrectomy: a prospective multicenter study in Spain.

BACKGROUND: Major concerns years after the sleeve gastrectomy (SG) include weight regain, development of hiatal hernia (HH) and gastroesophageal reflux disease, with esophagitis and Barrett's esophagus (BE). Both problems could be related, and the incidence of asymptomatic patients is troubling. OBJECTIVE: To study the incidence of reflux symptoms, esophagitis, BE, HH, and asymptomatic pathology and their relationship with weight regain in patients 5 years after undergoing SG at different bariatric centers in Spain. SETTING: Public and private hospitals with bariatric surgery units. METHODS: Prospective, multicenter, nonrandomized study involving 13 Spanish hospitals with a cumulative experience of 4,500 patients having undergone the SG procedure and patients who had been subjected to the procedure at least 5 years previously along with preoperative gastroscopy. The clinical history, preoperative gastroscopy, and technical details of the SG were recorded. A specific clinical questionnaire was given that recorded the intake volume, perception of satiety, and gastroesophageal reflux (GER) symptoms. Gastroscopy, pH-metry, and manometry studies were carried out, and the data were analyzed statistically. The study has been authorized by the official Spanish ethics committee CEI/CEIm Hospital Universitario Gran Canaria Dr Negrín (code 2019-216-1). RESULTS: One hundred and five patients who underwent SG and who had with at least 5 years of follow-up were included. All procedures were performed laparoscopically. The mean age of patients was 51.1 years, and 70.5% were women. The mean characteristics of the SG procedure were a 37.2F probe, at 4.6 cm from the pylorus, and a crura closure was performed in 5 cases. There were no major complications (Clavien-Dindo grade >3) or deaths. The average preoperative body mass index was 46.3 kg/m2, the minimum reached was 20.6 kg/m2, whereas the average after 5 years was of 34.5 kg/m2. GER, HH, and esophagitis symptoms went from 17.1%, 28.6%, and 5.7%, respectively, before the SG to 76%, 30.5%, and 31.4%, respectively, 5 years after the procedure. Symptoms persisted over the years in 37.1% of cases and presented de novo in 52.8% of cases. Fifty-three percent of manometries (n = 27, total 51) and 64% of pH-metries (n = 32, total 53; DeMeester average score was 65) were pathologic 5 years after the procedure. Concerning gastroscopies, 5 years after the procedure, HH was found in 33 patients (30.5% of total) and esophagitis in 32 patients (31.4% of total). Eighty patients (76%) had GER symptoms, and 25 patients (24%) were asymptomatic. Only 1 patient (.9%) developed BE. CONCLUSIONS: Our study has confirmed a high rate of both persistent and de novo esophagitis and hiatal hernia, many of which were asymptomatic, 5 years after SG had been performed. Weight regain and a striking increase in gastric capacity are risk factors indicative of esophagitis, even when patients are asymptomatic. We consider a control gastroscopy and the preventive use of proton pump inhibitors necessary in these cases regardless of symptoms. We recommend that a control gastroscopy should be performed in all cases regardless of symptoms 5 years after SG. Further studies are needed to validate these recommendations.

Modification of Thin Film Composite Membrane by Chitosan-Silver Particles to Improve Desalination and Anti-Biofouling Performance.

Reverse osmosis (RO) desalination is a technology that is commonly used to mitigate water scarcity problems; one of its disadvantages is the bio-fouling of the membranes used, which reduces its performance. In order to minimize this problem, this study prepared modified thin film composite (TFC) membranes by the incorporation of chitosan-silver particles (CS-Ag) of different molecular weights, and evaluated them in terms of their anti-biofouling and desalination performances. The CS-Ag were obtained using ionotropic gelation, and were characterized by Fourier transform infrared spectroscopy (FTIR), high-resolution scanning electron microscopy (HR-SEM), energy-dispersive X-ray spectroscopy (EDX), thermogravimetric analysis (TGA) and dynamic light scattering (DLS). The modified membranes were synthetized by the incorporation of the CS-Ag using the interfacial polymerization method. The membranes (MCS-Ag) were characterized by Fourier transform infrared spectroscopy (FTIR), atomic force microscopy (AFM) and contact angle. Bactericidal tests by total cell count were performed using Bacillus halotolerans MCC1, and anti-adhesion properties were confirmed through biofilm cake layer thickness and total organic carbon (%). The desalination performance was defined by permeate flux, hydraulic resistance, salt rejection and salt permeance by using 2000 and 5000 mg L-1 of NaCl. The MCS-Ag-L presented superior permeate flux and salt rejection (63.3% and 1% higher, respectively), as well as higher bactericidal properties (76% less in total cell count) and anti-adhesion capacity (biofilm thickness layer 60% and total organic carbon 75% less, compared with the unmodified membrane). The highest hydraulic resistance value was for MCS-Ag-M. In conclusion, the molecular weight of CS-Ag significantly influences the desalination and the antimicrobial performances of the membranes; as the molecular weight decreases, the membranes' performances increase. This study shows a possible alternative for increasing membrane useful life in the desalination process.

Ultrastructural changes and immunolocalization of P-selectin in platelets from patients with major depression.

Depression is considered an important risk factor in patients with cardiovascular disease (CVD). Although the biological mechanism is unknown, it has been suggested that hyperactivity of platelets may have an important role in the onset and evolution of cardiovascular damage. The goals of this study were to evaluate by transmission electron microscopy and immunohistochemistry the presence of ultra-structural variations in platelets from individuals with recent diagnosis of major depression disease (MDD, patients without previous anti-depressant treatment and from healthy control subjects.). Platelets from depressed patients had a greater proportion of dendritic forms compared with those obtained from control subjects. Morphological changes, such as dilation of open canalicular and dense tubular systems, platelet vacuolization, electrodense pattern of membranes, and a different immunolocalization of P-selectin were observed in the platelets from depressed patients compared with those isolated from healthy subjects. Our results revealed ultra-structural changes in platelets isolated from patients with MDD suggestive of enhanced platelet activation.

An association between glycine and insulin levels is observed in patients with pulmonary tuberculosis and type 2 diabetes.

BACKGROUND & AIMS: Adequate nutrition from which amino acids are part gives us protection against infectious or metabolic diseases. In particular, glycine has immunomodulatory properties and is a secretagogue of insulin. However, its absorption rate or plasma levels are impaired in bacterial infection or high glucose levels. The aim of this study was to evaluate the association between glycine and insulin plasma levels in patients with pulmonary tuberculosis (PTB) and type 2 diabetes mellitus (DM2). METHODS: Plasma levels of insulin and glycine were determined in four groups: 1) patients with PTB; 2) patients with PTB-DM2; 3) household contacts with DM2 (C-DM2), and 4) healthy household contacts (H-C). Likewise, we analyzed the plasma levels of glucose, serine, arginine, lysine, taurine, and glutamic acid. RESULTS: We observed significant differences in the glycine levels between PTB and PTB-DM2 vs C-DM2 and H-C groups (P < 0.05). We observed also important differences in insulin and glucose levels after comparisons between PTB, PTB-DM2, and C-DM2 vs. H-C groups (P < 0.05). A correlation between glycine and insulin levels in the PTB (r = 0.326) and PTB-DM2 (r = 0.318) groups was found. CONCLUSION: Our results showed a significant association between glycine and insulin plasma levels in patients with PTB and PTB-DM2, which suggests that the determination of glycine levels could be used as a reference test to evaluate both pathologic conditions. An additional support to the above is that significant changes in the glucose levels in these groups were observed, too.

Antinociceptive activity of Tilia americana var. mexicana inflorescences and quercetin in the formalin test and in an arthritic pain model in rats.

Tilia species are well known around the world for their properties in traditional medicine. Antinociceptive activity of hexane, methanol and aqueous extracts from Tilia americana var. mexicana inflorescences was evaluated in the pain-induced functional impairment model in rats (PIFIR). A preliminar 300 mg/kg dosage of aqueous extracts i.p., but not the same dose of methanol or hexane extract, produced an antinociceptive response in rats similar to that of tramadol (17.8 mg/kg i.p.). A dose-response curve from aqueous extract allowed the determination of ED(50) = 364.97 mg/kg in comparison to ED(50) = 10.35 mg/kg for tramadol in this model. A previous HPLC-DAD analysis corroborated by an HPLC-MS technique in this study demonstrated the flavonoid composition in this Tilia aqueous extract revealing the presence of glycosides mainly derived from quercetin. Thus, Tilia aqueous extract and quercetin were tested at 30 and/or 100 mg/kg dosages i.p. in the PIFIR and formalin models producing a significant and dose-dependent antinociceptive response resembling that produced by a total and a partial agonist of 5-HT(1A) receptors like 8-OH-DPAT (0.1 mg/kg, s.c.) and buspirone (5 mg/kg, i.p.), respectively. In all the treatments, antinociceptive response was inhibited in the presence of WAY 100635 (0.12 mg/kg, i.p.). Our results support the analgesic activity of T. americana var. mexicana inflorescences attributed by folk medicine; they also indicate that quercetin is partly responsible for this pharmacological activity that is likely mediated by serotonin 5-HT(1A) receptors.

Selective synthesis, reactivity and luminescence of unsymmetrical bis-cyclometalated Pt(iv) complexes.

Pt(ii) complexes cis-N,N-[PtCl(C^N)(N'^C'H)], where C^N represents a monocyclometalated 2,6-diaryl- or 2-arylpyridine ligand and N'^C'H is an N-coordinated 2-arylpyridine, are selectively obtained from bridge-cleavage reactions of dimers [Pt2(µ-Cl)2(C^N)2] with excess N'^C'H at room temperature; isolation and characterization of derivatives of this kind is reported for the first time. Oxidation with PhICl2 affords Pt(iv) complexes [PtCl2(C^N)(C'^N')], bearing two cyclometalated ligands in an unsymmetrical arrangement. The abstraction of the two chlorides using AgOTf at 120 °C in the presence of an additional 2-arylpyridine ligand leads to mer isomers of tris-cyclometalated Pt(iv) complexes if C^N derives from a 2-arylpyridine, whereas it results in a reductive C-C coupling if C^N is a monocyclometalated 2,6-diarylpyridine. Complexes [PtCl2(C^N)(C'^N')] show phosphorescence in frozen PrCN glasses arising from essentially 3LC excited states localized on the cyclometalated ligand with the lowest π-π* transition energy. The combined photophysical data and computational results substantiate a variable degree of MLCT admixture into the emitting state depending on the atom trans to the metalated carbon of the chromophoric ligand (Cl or N), which has an appreciable effect on the characteristics of the observed luminescence.

Variations in circulating cytokine levels during 52 week course of treatment with SSRI for major depressive disorder.

Major depressive disorder (MDD) is a psychiatric condition characterized by hypercortisolism and variations in circulatory cytokines. Previously it has been reported that administration of selective serotonin reuptake inhibitors (SSRI) in MDD patients modify cortisol and cytokine levels but these studies only evaluated changes over a short time period. This work reports the long-term effects of administration of SSRI on the cortisol levels and pro-/anti-inflammatory cytokine profile in a group of MDD patients treated for 52 weeks. A total of 31 patients diagnosed with MDD received anti depressant treatment with SSRI. HDRS and BDI were administered over a year, and levels of interleukin IL-1beta, IL-10, IL-2, IFN-gamma, IL-4, IL-13, and 24-h urine cortisol were determined at weeks (W) 0, 5, 20, 36 and 52 of treatment. Before treatment we found high levels of cortisol, IL-4, IL-13 (Th2) and IL-10 in MDD patients when compared with healthy volunteers. At W20 psychiatric scales indicated a remission of the depressive episode concomitantly with increments in IL-2 and IL-1beta but without changes in cortisol. Towards the end of the treatment (W52) we observed a significant reduction (p<0.01) in cortisol levels, with an increment in IL-1beta and IFN-gamma and a decrease in Th2 cytokines. Our results suggest that depressed patients only reach a partial reestablishment of HPA axis function after the long-term administration of SSRI.

Th2 cytokine response in Major Depressive Disorder patients before treatment.

In Major Depressive Disorder (MDD), the neuroendocrine and immune systems interactions are impaired. We investigated the pro/anti-inflammatory Th1/Th2 cytokine balance in MDD patients and in non-depressed control group. The MDD subjects showed higher levels of cortisol and TNF-alpha, increased CD3+CD8+ and NK percentages, diminished B cell counts and no significant variations in CD3+CD4+ lymphocyte. Moreover, higher levels of IL-4 and IL-13 (Th2) and significantly lower measurements of IL-2 and IFN-gamma (Th1) cytokines were also observed in the MDD group. Overall, we propose that all these changes could be related to the elevated cortisol levels seen in the MDD patients. Further studies are necessary to explore these findings and its implication in future therapeutic approach of MDD patients.

Field accumulative behavior of organochlorine pesticides. The role of crabs and sediment characteristics in coastal environments.

The influence of intertidal crab beds on the concentrations of organochlorine (OC) pesticides in sediment was studied in two different coastal environments in Argentina. Samples of male burrowing crabs (Chasmagnathus granulatus) were collected for this study. Our field data showed lower bioaccumulation of OC pesticides in crabs from sediments with a higher total organic carbon (TOC) and higher clay content. Thus, concentrations in crabs depend on the physico-chemical characteristics of the sediment where they live more than on the OC pesticide concentrations in the environment. The distribution patterns in sediment from inside and outside crab burrows were similar for both coastal areas being HCHs > or = gamma-chlordane > p,p'-DDE for San Antonio Bay (SAO), and HCHs > p,p'-DDE > or = gamma-chlordane for Mar Chiquita (MCh) coastal lagoon. OC pesticide concentrations in sediment were significantly lower inside than outside crab burrows, irrespective of the sediment physico-chemical characteristics due to the bioturbation activity of C. granulatus.

Evaluation of conventionally and organically produced vegetables for high lipophilic organochlorine pesticide (OCP) residues.

The occurrence and distribution of highly hydrophobic organochlorine pesticide (OCP) in vegetables cultivated under organic and conventional conditions were evaluated. OCP residues in aerial and subterranean tissues of two varieties of lettuce and chard together with the soil where they grown were GC-ECD analyzed. SigmaDDTs>SigmaChlordane>SigmaHeptachlor>SigmaAldrins was the OCP distribution pattern in all samples. Conventional soils had higher OCP residues than organic one, even though levels were bellow 5 ng/g dry weight, indicative of low polluted agricultural environments. Vegetables accumulated OCP efficiently with residue levels 4x to 45x fold greater than those of soils. OCP tissue-dependent distribution was found to be upon the physicochemical characteristics of the pollutants (Koa and Kow). Lettuce showed a high variability in pesticide uptake regarding varieties and tillage practices. In spite of analyzed pesticides are banned or restricted, edible tissues of vegetables from both farms showed detectable residues of these compounds even though at levels below the allowed by the Codex Alimentarius. Thus, environmental conditions like presence or absence of trees, hedgerows or nearby to conventional farms influence on OCP occurrence and levels in vegetables organically grown.

Methodologic pitfalls in measurement of 5-hydroxytriptamine uptake transporters in human platelets by [3H]-paroxetine binding assay.

BACKGROUND: Studies in platelet of 5-HT uptake transporters have been performed using binding assay methodology designed for ligand-receptor interactions; however, uptake transporters present requirements that may question the validity of these particular binding assays. METHODS: To explore methodologic aspects that may be crucial to the validity of these assays, we studied the binding of [3H]-paroxetine to platelet membranes of healthy subjects under different conditions of time, temperature, and protein concentrations. RESULTS: A correlation between protein concentration in incubation media and percentage of specific binding of [3H]-paroxetine was found: the lower the protein concentrations (10 and 20 microg/mL) in incubation media, the lower the percentage of specific [3H]-paroxetine binding. Moreover, low specificity in [3H]-paroxetine binding affected Bmax values obtained in saturation binding experiments. CONCLUSIONS: The use of low protein concentrations could affect Bmax values in binding assays of 5-HT uptake transporters. This may induce confusing interpretation of data in clinical experiments that use human platelets to explore the participation of serotonin in depressed patients.

Pharmacokinetic study of carbamazepine and its carbamazepine 10,11-epoxide metabolite in a group of female epileptic patients under chronic treatment.

BACKGROUND: Although epileptic crises are equally frequent in women and men, several factors cause female epileptics to present a series of gender-specific problems. To date, few studies have been published on the kinetics of carbamazepine (CBZ) and carbamazepine 10,11-epoxide (CBZ-E) active metabolite in a Mexican population, and no information for epileptic women of reproductive age is available. The aim of the present work was to study the pharmacokinetic behavior of this group of women during steady state. METHODS: Fourteen epileptic women under chronic treatment receiving only the anticonvulsant CBZ to control their crises were studied. A blood sample was taken before breakfast, before the morning dose of 200 mg, and after the dose at 1, 2, 3, 4, 5, and 8 h. Serum was separated by centrifugation at 1,350 x g. Serum concentrations of carbamazepine (CBZ) and of the metabolite carbamazepine 10,11-epoxide (CBZ-E) were measured by HPLC. Pharmacokinetic parameters were calculated by statistical moment method after obtaining serum concentrations. RESULTS: Maximum time (T(max)) for CBZ was reached at 2.72+/-0.71 h and for CBZ-E, it was 3.60+/-0.79 h. C(max) for CBZ was 7.30+/-2.30 microg/mL, while C(min) for CBZ was 6.30+/-2.49. Maximum serum values for CBZ-E were 1.01+/-0.57, equivalent to 13.80% of CBZ; t(12) value for CBZ and CBZ-E was 18.20 and 16.10 h, respectively. AUC values for CBZ and metabolite were 70.33+/-17.10 microg/L/h and 9.20+/-2.50 microg/L/h, respectively. CBZ and CBZ-E clearance did not show differences and were 0.37 mL/kg/min and 0.40 mL/kg/min, respectively. Extraction index for serum concentrations of CBZ and CBZ-E AUC(CBZ)/AUC(CBZ-E) was 0.13; positive correlation was observed between serum concentrations of CBZ and E-CBZ, with r=0.94. CONCLUSIONS: The schedule we suggest for therapeutic monitoring of serum concentrations of CBZ in chronic treatments is 3 h for maximum peak concentration of C(max) after dose administration and for minimum peak concentration, C(min) prior to subsequent administration of the dose.

Occurrence and distribution of organochlorine pesticides (OCPs) in tomato (Lycopersicon esculentum) crops from organic production.

Organochlorine pesticides (OCPs) were quantified by GC-ECD in tomato (Lycopersicon esculentum) during a vegetation period. Plants were harvested at 15, 60, and 151 days after seed germination. Leaves, stem, roots, and fruit (peel and flesh) were analyzed separately. The results showed that tomato plants were able to accumulate OCPs from soils, and a trend to reach the equilibrium among tissues at mature stages was also observed. Endosulfans comprised the main OCP group, probably due to its spray during summer months in the surrounding areas. Banned pesticides such as DDTs, heptachlor, and dieldrin were found. OCPs levels in the fruit were below the maximum residues limits (MRL) considered by the Codex Alimentarius. DDE/DDT and alpha-/gamma-HCH ratios of <1 would indicate recent inputs of DDT and lindane in the environment. The occurrence of OCPs in the study farm, where agrochemicals have never been used, is a result of atmospheric deposition of those pesticides.