Elevated mercury exposure in bird communities inhabiting Artisanal and Small-Scale Gold Mining landscapes of the southeastern Peruvian Amazon.

Artisanal and Small-Scale Gold Mining (ASGM) represents a significant source of anthropogenic mercury emissions to the environment, with potentially severe implications for avian biodiversity. In the Madre de Dios department of the southern Peruvian Amazon, ASGM activities have created landscapes marred by deforestation and post-mining water bodies (mining ponds) with notable methylation potential. While data on Hg contamination in terrestrial wildlife remains limited, this study measures Hg exposure in several terrestrial bird species as bioindicators. Total Hg (THg) levels in feathers from birds near water bodies, including mining ponds associated with ASGM areas and oxbow lakes, were analyzed. Our results showed significantly higher Hg concentrations in birds from ASGM sites with mean ± SD of 3.14 ± 7.97 µg/g (range: 0.27 to 72.75 µg/g, n = 312) compared to control sites with a mean of 0.47 ± 0.42 µg/g (range: 0.04 to 1.89 µg/g, n = 52). Factors such as trophic guilds, ASGM presence, and water body area significantly influenced feather Hg concentrations. Notably, piscivorous birds exhibited the highest Hg concentration (31.03 ± 25.25 µg/g, n = 12) exceeding known concentrations that affect reproductive success, where one measurement of Chloroceryle americana (Green kingfisher; 72.7 µg/g) is among the highest ever reported in South America. This research quantifies Hg exposure in avian communities in Amazonian regions affected by ASGM, highlighting potential risks to regional bird populations.

Striatal Protection in nNOS Knock-Out Mice After Quinolinic Acid-Induced Oxidative Damage.

Under pathological conditions, nitric oxide can become a mediator of oxidative cellular damage, generating an unbalance between oxidant and antioxidant systems. The participation of neuronal nitric oxide synthase (nNOS) in the neurodegeneration mechanism has been reported; the activation of N-methyl-D-aspartate (NMDA) receptors by agonist quinolinic acid (QUIN) triggers an increase in nNOS function and promotes oxidative stress. The aim of the present work was to elucidate the participation of nNOS in QUIN-induced oxidative stress in knock-out mice (nNOS-/-). To do so, we microinjected saline solution or QUIN in the striatum of wild-type (nNOS +/+), heterozygote (nNOS+/-), and knock-out (nNOS-/-) mice, and measured circling behavior, GABA content levels, oxidative stress, and NOS expression and activity. We found that the absence of nNOS provides a protection against striatal oxidative damage induced by QUIN, resulting in decreased circling behavior, oxidative stress, and a partial protection reflected in GABA depletion. We have shown that nNOS-derived NO is involved in neurological damage induced by oxidative stress in a QUIN-excitotoxic model.

Clinical Characteristics in Patients with Rheumatoid Arthritis: Differences between Genders.

OBJECTIVE: To compare the clinical characteristics of a group of men and women with rheumatoid arthritis (RA) and determine the differences between genders. MATERIALS AND METHODS: A descriptive and comparative cross-sectional study was developed with a group of 50 men and a control group of 50 women with RA, from a rheumatology center in the city of Guayaquil, Ecuador. Data collected included clinical manifestations, comorbidities, treatment, and disease activity. Clinical and activity differences between sexes were analyzed. RESULTS: Women were more devoted to housework (66%), while men consumed more tobacco (34%) and alcohol (38%). Fatigue (60%), loss of appetite (54%), and weight loss (44%) were more common in women. No differences were found in comorbidities or treatment. Women had higher values of DAS-28 (3.4 vs 2.5), HAQ-DI (1.1 vs 0.4), ESR (33.0 vs 23.2), painful joints (8 vs 3), swollen joints (6 vs 2), and overall physician assessment (3 vs 2). CONCLUSION: The results are similar to other publications that establish that women have a more aggressive disease with greater activity of the disease and disability.

Parameters and functional analysis of the deep epaxial muscles in the thoracic, lumbar and sacral regions of the equine spine.

The epaxial muscles produce intervertebral rotation in the transverse, vertical and axial axes. These muscles also counteract the movements induced by gravitational and inertial forces and movements produced by antagonistic muscles and the intrinsic muscles of the pelvic limb. Their fascicles are innervated by the dorsal branch of the spinal nerve, which corresponds to the metamere of its cranial insertion in the spinous process. The structure allows the function of the muscles to be predicted: those with long and parallel fibres have a shortening function, whereas the muscles with short and oblique fibres have an antigravity action. In the horse, the multifidus muscle of the thoracolumbar region extends in multiple segments of two to eight vertebral motion segments (VMS). Functionally, the multifidus muscle is considered a spine stabiliser, maintaining VMS neutrality during spine rotations. However, there is evidence of the structural and functional heterogeneity of the equine thoracolumbar multifidus muscle, depending on the VMS considered, related to the complex control of the required neuromuscular activity. Osteoarticular lesions of the spine have been directly related to asymmetries of the multifidus muscle. The lateral (LDSM) and medial (MDSM) dorsal sacrocaudal muscles may be included in the multifidus complex, the function of which is also unclear in the lumbosacral region. The functional parameters of maximum force (Fmax ), maximum velocity of contraction (Vmax ) and joint moment (M) of the multifidus muscles inserted in the 4th, 9th, 12th and 17th thoracic and 3rd and 4th lumbar vertebrae of six horses were studied postmortem (for example: 4MT4 indicates the multifidus muscle that crosses four metameres with cranial insertion in the T4 vertebra). Furthermore, the structural and functional characteristics of LDSM and MDSM were determined. Data were analysed by analysis of variance (anova) in a randomised complete block design (P ≤ 0.05). For some muscles, the ordering of Vmax values was almost opposite to that of Fmax values, generally indicating antigravity or dynamic functions, depending on the muscle and VMS. The muscles 3MT12, 3ML3 and 4ML4 exhibited high Fmax and low Vmax values, indicating a stabilising action. The very long 7MT4 and 8MT4 multifidus had low Fmax and high Vmax values, suggesting a shortening action. However, some functional characteristics of interest did not fall within these general observations, also indicating a dual action. In summary, the results of the analysis of various structural and functional parameters confirm the structural and functional heterogeneity of the equine thoracolumbar multifidus complex, depending on the VMS, regardless of the number of metameres crossing each fascicle. To clarify the functions of the equine multifidus muscle complex, this study aimed to assess its functional parameters in thoracolumbar VMSs with different movement characteristics and in the MDSM and LDSM muscles, hypothesising that the functional parameters vary significantly when the VMS is considered.

Diagnostic performance of cytology for assessment of hepatic lipid content in dairy cattle.

The objective of our study was to characterize the diagnostic performance of cytology for assessing hepatic lipid content (HLC) in dairy cows by comparing microscopic evaluation of lipid vacuolation in touch imprint slide preparations of liver biopsies with quantitative measurement of triglyceride concentration ([TG]; mg/mg of wet weight) in paired biopsy samples. Our study also sought to compare the diagnostic performance of liver cytology, plasma nonesterified fatty acid concentration ([NEFA]), and plasma ß-hydroxybutyrate concentration ([BHB]) derived from a measurement performed on whole blood, for assessing HLC. Chemical extraction of TG from liver tissue remains the gold standard for quantifying HLC, largely because available blood tests, although useful for detecting some types of pathology, such as increased lipid mobilization, ketosis, or hepatocellular injury, are nonspecific as to etiology. Veterinary practitioners can sample bovine liver for cytological evaluation in a fast, minimally invasive, and inexpensive manner. Thus, if highly predictive of HLC, cytology would be a practical diagnostic tool for dairy veterinarians. In our study, liver biopsy samples from Holstein cows (219 samples from 105 cows: 52 from cows 2 to 20 d prepartum, 105 from cows 0 to 10 d in milk, 62 from cows 18 to 25 d in milk) were used to prepare cytology slides and to quantify [TG] using the Folch extraction method followed by the Hantzch condensation reaction and spectrophotometric measurement. An ordinal scale (0-4) based on amount of hepatocellular cytoplasm occupied by discrete clear vacuoles was used by 3 blinded, independent observers to rank HLC in Wright-Giemsa-stained slides. Interobserver agreement in cytology scoring was good. Corresponding plasma [NEFA] and [BHB] measurements were available for 187 and 195 of the 219 samples, respectively. Liver [TG] correlated more strongly with cytology score than with NEFA or BHB, and receiver operating characteristic curve analysis showed that cytology had better diagnostic performance than either NEFA or BHB for correctly categorizing [TG] at thresholds of 5, 10, and 15%. Hepatic lipidosis in high-producing dairy cows is of major clinical and economic importance, and this study demonstrates that cytology is an accurate means of assessing HLC. Additional work is indicated to evaluate the diagnostic utility of liver cytology.

Ratcheting droplet pairs.

Millimetric droplets may be levitated on the surface of a vibrating fluid bath. Eddi et al. [Europhys. Lett. 82, 44001 (2008)] demonstrated that when a pair of levitating drops of unequal size are placed nearby, they interact through their common wavefield in such a way as to self-propel through a ratcheting mechanism. We present the results of an integrated experimental and theoretical investigation of such ratcheting pairs. Particular attention is given to characterizing the dependence of the ratcheting behavior on the droplet sizes and vibrational acceleration. Our experiments demonstrate that the quantized inter-drop distances of a ratcheting pair depend on the vibrational acceleration, and that as this acceleration is increased progressively, the direction of the ratcheting motion may reverse up to four times. Our simulations highlight the critical role of both the vertical bouncing dynamics of the individual drops and the traveling wave fronts generated during impact on the ratcheting motion, allowing us to rationalize the majority of our experimental findings.

Strategies to manage hepatitis C virus infection disease burden-Volume 4.

The hepatitis C virus (HCV) epidemic was forecasted through 2030 for 17 countries in Africa, Asia, Europe, Latin America and the Middle East, and interventions for achieving the Global Health Sector Strategy on viral hepatitis targets-"WHO Targets" (65% reduction in HCV-related deaths, 90% reduction in new infections and 90% of infections diagnosed by 2030) were considered. Scaling up treatment and diagnosis rates over time would be required to achieve these targets in all but one country, even with the introduction of high SVR therapies. The scenarios developed to achieve the WHO Targets in all countries studied assumed the implementation of national policies to prevent new infections and to diagnose current infections through screening.

Structural and functional characteristics of the thoracolumbar multifidus muscle in horses.

The multifidus muscle fascicles of horses attach to vertebral spinous processes after crossing between one to six metameres. The fascicles within one or two metameres are difficult to distinguish in horses. A vertebral motion segment is anatomically formed by two adjacent vertebrae and the interposed soft tissue structures, and excessive mobility of a vertebral motion segment frequently causes osteoarthropathies in sport horses. The importance of the equine multifidus muscle as a vertebral motion segment stabilizer has been demonstrated; however, there is scant documentation of the structure and function of this muscle. By studying six sport horses postmortem, the normalized muscle fibre lengths of the the multifidus muscle attached to the thoracic (T)4, T9, T12, T17 and lumbar (L)3 vertebral motion segments were determined and the relative areas occupied by fibre types I, IIA and IIX were measured in the same muscles after immunohistochemical typying. The values for the normalized muscle fibre lengths and the relative areas were analysed as completely randomized blocks using an anova (P ≤ 0.05). The vertebral motion segments of the T4 vertebra include multifidus bundles extending between two and eight metameres; the vertebral motion segments of the T9, T12, T17 and L3 vertebrae contain fascicles extending between two and four metameres The muscle fibres with high normalized lengths that insert into the T4 (three and eight metameres) vertebral motion segment tend to have smaller physiological cross-sectional areas, indicating their diminished capacity to generate isometric force. In contrast, the significantly decreased normalized muscle fibre lengths and the increased physiological cross-sectional areas of the fascicles of three metameres with insertions on T9, T17, T12, L3 and the fascicles of four metameres with insertions on L3 increase their capacities to generate isometric muscle force and neutralize excessive movements of the vertebral segments with great mobility. There were no significant differences in the values of relative areas occupied by fibre types I, IIA and IIX. In considering the relative areas occupied by the fibre types in the multifidus muscle fascicles attached to each vertebral motion segment examined, the relative area occupied by the type I fibres was found to be significantly higher in the T4 vertebral motion segment than in the other segments. It can be concluded that the equine multifidus muscle in horses is an immunohistochemically homogeneous muscle with various architectural designs that have functional significance according to the vertebral motion segments considered. The results obtained in this study can serve as a basis for future research aimed at understanding the posture and dynamics of the equine spine.

Nailfold capillaroscopy in diabetes mellitus.

INTRODUCTION: Diabetes mellitus (DM) is characterized by chronic hyperglycemia states and the development of specific microvascular disorders such as retinopathy and nephropathy. Conventional methods are used to study the vascular compromise of this entity, however, the use of capillaroscopy for the evaluation of capillary microarchitecture is not frequently used. METHODS AND MATERIALS: Observational and descriptive study of 65 patients with an established diagnosis of DM and a control group that underwent an initial capillaroscopy examination. The parameters considered were: Capillary diameter (ectasia and giant capillaries), cross-linked, tortuous, arborified capillaries, avascular zones, haemorrhages, dominant morphology, visibility of the subpapillary venous plexus (SPVP), cuticulitis and SD pattern. RESULTS: Capillaroscopy was performed in 65 patients, the findings were: tortous capillaries (63%), crosslinked capillaries (59%), avascular areas (48%), ectasias (39%), giant capillaries (11%). The capillaroscopic findings were evident in the majority of the studied population, 83%, compared to 17% who did not have capillaroscopic alterations. CONCLUSION: Significant capillaroscopic changes were demonstrated in patients with DM, in turn, we described a specific pattern consisting of: capillary dilatation, avascular zones and tortuous capillaries. Patients with more comorbidities and evolution of the disease showed greater microvascular damage.

Determination of Vitamin D Status in a Population of Ecuadorian Subjects.

INTRODUCTION: Vitamin D is a preprohormone known to play a key role in phosphocalcic metabolism; its main source comes from the synthesis at the skin level by ultraviolet (UV) radiation. OBJECTIVE: The purpose of this study was to determine the levels of vitamin D in an Ecuadorian population. MATERIALS AND METHODS: Retrospective study of Ecuadorian subjects from the city of Guayaquil, who had an initial study of 25 (OH)-D serum, as the indicator of Vitamin D status, in the period of 2015-2016. RESULTS: A total of 269 Ecuadorian subjects were analyzed, with a mean age of 54.73 ± 16.58; 85% (229) were females and 15% (41) males; mean vitamin D was 27.29 ± 10.12 ng/dl [6.41-88.74]; 70% of the population showed levels below 30 ng/dL of vitamin D, whereas only 30% (81) had normal values. 69% (185) had levels between 29 and 10 ng/dl and 1% (3) levels below 10 ng/dl. High levels of vitamin D were evidenced in the summer months in relation to the winter months. CONCLUSION: It is evident that, despite the location of Ecuador and the intensity of UV rays it receives throughout the year, Ecuadorian subjects have insufficient levels of vitamin D.

Pharmacological targeting of histamine H4 receptor in periodontal disease.

OBJECTIVE: The objective of this study was to investigate whether histamine H4 receptor (H4 R) antagonists could prevent experimental periodontitis (EP)-induced histological, functional and inflammatory alterations in submandibular gland (SMG), periodontal bone and gingiva. METHODS: Bilateral EP was induced for 2 weeks in anaesthetized male rats. The effect of systemic and local administration of H4 R antagonists (JNJ7777120, JNJ10191584) on histopathology and functionality of SMG, bone loss and gingival inflammation was evaluated. RESULTS: The subcutaneous administration of JNJ7777120 prevented periodontitis-induced SMG histological injury, reducing vacuolization and apoptosis and additionally reversed the increased prostaglandin E2 (PGE2) levels in SMG while it partially reversed the methacholine-induced salivation reduction produced by periodontitis. JNJ7777120 attenuated bone loss and the increased PGE2 levels and inflammatory infiltration in gingival tissue of rats with periodontitis. Finally, local administration of JNJ7777120 and JNJ10191584 was also beneficial for improving periodontal parameters. CONCLUSIONS: H4 receptor antagonists are able to ameliorate periodontitis-induced injury on SMG, gingival tissue and bone structure, suggesting that pharmacological targeting of H4 R could be an attractive strategy to improve periodontal health.

CRISPR-Cas9-mediated gene knockout in primary human airway epithelial cells reveals a proinflammatory role for MUC18.

Targeted knockout of genes in primary human cells using CRISPR-Cas9-mediated genome-editing represents a powerful approach to study gene function and to discern molecular mechanisms underlying complex human diseases. We used lentiviral delivery of CRISPR-Cas9 machinery and conditional reprogramming culture methods to knockout the MUC18 gene in human primary nasal airway epithelial cells (AECs). Massively parallel sequencing technology was used to confirm that the genome of essentially all cells in the edited AEC populations contained coding region insertions and deletions (indels). Correspondingly, we found mRNA expression of MUC18 was greatly reduced and protein expression was absent. Characterization of MUC18 knockout cell populations stimulated with TLR2, 3 and 4 agonists revealed that IL-8 (a proinflammatory chemokine) responses of AECs were greatly reduced in the absence of functional MUC18 protein. Our results show the feasibility of CRISPR-Cas9-mediated gene knockouts in AEC culture (both submerged and polarized), and suggest a proinflammatory role for MUC18 in airway epithelial response to bacterial and viral stimuli.

Effect of tibolone on dendritic spine density in the rat hippocampus.

INTRODUCTION: Oestrogen deficiency produces oxidative stress (OS) and changes in hippocampal neurons and also reduces the density of dendritic spines (DS). These alterations affect the plastic response of the hippocampus. Oestrogen replacement therapy reverses these effects, but it remains to be seen whether the same changes are produced by tibolone (TB). The aim of this study was to test the neuroprotective effects of long-term oral TB treatment and its ability to reverse DS pruning in pyramidal neurons (PN) of hippocampal area CA1. METHODS: Young Sprague Dawley rats were distributed in 3 groups: a control group in proestrus (Pro) and two ovariectomised groups (Ovx), of which one was provided with a daily TB dose (1mg/kg), OvxTB and the other with vehicle (OvxV), for 40 days in both cases. We analysed lipid peroxidation and DS density in 3 segments of apical dendrites from PNs in hippocampal area CA1. RESULTS: TB did not reduce lipid peroxidation but it did reverse the spine pruning in CA1 pyramidal neurons of the hippocampus which had been caused by ovariectomy. CONCLUSIONS: Oestrogen replacement therapy for ovariectomy-induced oestrogen deficiency has a protective effect on synaptic plasticity in the hippocampus.

[Translated article] Postsurgical analgesic efficacy by the intra-articular administration of ropivacaine with dexmedetomidine versus simple ropivacaine in patients undergoing knee arthroscopy.

The effective relief of postsurgical pain in patients undergoing knee arthroscopy is important to allow the initiation of activities of daily living. The objective of this study is to demonstrate the analgesic efficacy of dexmedetomidine as an adjuvant added to ropivacaine by the intra-articular route. METHOD: Seventy patients underwent knee arthroscopy which were randomly assigned into two groups (n=35). The RD group received ropivacaine 1.5mg/kg plus dexmedetomidine 1µg/kg intra-articularly. Group R received ropivacaine 1.5mg/kg intra-articularly. The analgesic effect was evaluated by measuring the intensity of pain (VAS score) and the duration of analgesia. RESULTS: A longer duration of the analgesic effect was observed in the RD group (655min) compared to the R group (318min) being statistically significant (p=0.03). CONCLUSION: Dexmedetomidine as an adjuvant to intra-articular ropivacaine improves the quality and duration of postoperative analgesia in patients undergoing knee arthroscopy.

[Spinal cord stimulation in refractory complex regional pain syndrome. A prospective study]. / Estimulación medular en el síndrome de dolor regional complejo refractario. Un estudio prospectivo.

INTRODUCTION AND AIMS: The objective of treatment of complex regional pain syndrome is to relieve pain and restore function in the affected limb. The aim of this study is to evaluate spinal cord stimulation as a therapy for patients diagnosed with complex regional pain syndrome, for whom adequate pain control could not be achieved with other previous treatments. PATIENTS AND METHODS: A prospective study was conducted from 2018 to 2020. We included patients diagnosed with complex regional pain syndrome refractory to other treatments or techniques, classified by demographic data. Efficacy, functionality and opioid dependence in each patient were subsequently monitored for one year. RESULTS: Seven of the 13 patients (53.84%) included in the study achieved significant pain relief with spinal cord stimulation. Improvements in pain and functionality were obtained, and both were statistically significant (p < 0.001 and p = 0.003, respectively). Improvement in the Oswestry Disability Index/Neck Disability Index (ODI/NDI) was significantly associated with body mass index (BMI) (p = 0.011) and was lower as BMI increased. CONCLUSIONS: The results suggest that spinal cord stimulation is an effective therapeutic option for patients with CRPS refractory to other treatments. BMI and ODI/NDI also showed a significant correlation.

TITLE: Estimulación medular en el síndrome de dolor regional complejo refractario. Un estudio prospectivo.Introducción y objetivos. En el tratamiento del síndrome de dolor regional complejo se pretende aliviar el dolor y restaurar la función de la extremidad afectada. El objetivo de este estudio es evaluar la estimulación de la médula espinal como terapia para pacientes a quienes se les diagnosticó síndrome de dolor regional complejo, en los que no se ha podido conseguir un control adecuado del dolor con otros tratamientos previos. Pacientes y métodos. Se realizó un estudio prospectivo de 2018 a 2020. Se incluyó a pacientes diagnosticados de síndrome de dolor regional complejo refractario a otros tratamientos o técnicas, clasificados por datos demográficos. Posteriormente, se hizo seguimiento de la eficacia, la funcionalidad y la dependencia de opioides de cada paciente durante un año. Resultados. Siete de los 13 (53,84%) pacientes incluidos en el estudio consiguieron un alivio significativo de su dolor con la estimulación medular. Se obtuvo mejoría del dolor y de la funcionalidad, y ambas fueron estadísticamente significativas (p < 0,001 y p = 0,003, respectivamente). La mejoría en el Oswestry Disability Index/Neck Disability Index (ODI/NDI) se asoció significativamente con el índice de masa corporal (IMC) (p = 0,011) y fue menor cuanto mayor era el IMC. Conclusiones. Los resultados sugieren que la estimulación de la médula espinal es una opción terapéutica eficaz para pacientes con SDRC refractario a otros tratamientos. Además, el IMC y el ODI/NDI mostraron una correlación significativa.

Effect of environmental manganese exposure on verbal learning and memory in Mexican children.

Manganese (Mn) is an essential metal, but in excess it becomes neurotoxic. Children's developing nervous system may be especially vulnerable to the neurotoxic effects of overexposure to this metal. The aim of this study was to assess the effect of Mn exposure on verbal memory and learning in 7- to 11-year-old children. We tested 79 children living in the Molango Mn-mining district and 95 children from a non-exposed community in the same State of Mexico. The Children's Auditory Verbal Learning Test (CAVLT) was administered. Blood and hair samples were obtained to determine Mn concentrations using atomic absorption spectrophotometry. CAVLT performance was compared between the two groups and multilevel regression models were constructed to estimate the association between biomarkers of Mn exposure and the CAVLT scores. The exposed group presented higher hair and blood Mn (p<0.001) than the non-exposed group (median 12.6 vs. 0.6µg/g, 9.5vs. 8.0µg/L respectively), as well as lower scores (p<0.001) for all the CAVLT subscales. Hair Mn was inversely associated with most CAVLT subscales, mainly those evaluating long-term memory and learning (ß=-0.47, 95% CI -0.84, -0.09). Blood Mn levels showed a negative but non-significant association with the CAVLT scores. These results suggest that Mn exposure has a negative effect on children's memory and learning abilities.

Hypothyroidism reduces glutamate-synaptic release by ouabain depolarization in rat CA3-hippocampal region.

Thyroid hormones modulate the physiology of the hippocampus in humans, where glutamate plays an important role as neurotransmitter. The aim of this work was to study the effect of hypothyroidism on hippocampal glutamate extracellular levels, release, uptake, and synthesis. The effects of PDC (a glutamate transporter inhibitor) and ouabain (a Na(+) /K(+) -ATPase inhibitor) infusion on microdialysate glutamate and aspartate levels of CA3 hippocampal region were evaluated. Animals were assigned to one of the following groups: hypothyroid group (Hyp), receiving methimazole (anantithyroid drug); replacement group (Hyp + T(4) ), receiving antithyroid treatment plus thyroxine; and euthyroid control group (Eut). Dialysate fractions were collected every 15 min to determine basal glutamate levels for 1 hr. Then, PDC (10 mM) or ouabain (100 µM) was infused for 30 min. Results showed lower glutamate and aspartate basal levels in Hyp than in Eut groups. PDC infusion increased amino acids levels in all groups, whereas ouabain infusion increased glutamate and aspartate levels only in the Eut group. The infusion of tetrodotoxin (TTX; a voltage-gated sodium channel inhibitor) prevented the glutamate increase in euthyroid rats. The Hyp + T(4) group showed glutamate levels similar to those found in the Eut group. Additionally, glutaminase activity in hippocampus was lower in the Hyp group than in the Eut or Hyp + T(4) group. Results suggest that high-affinity glutamate transporters are not altered by hypothyroidism; however, decreased hypotyroidism reduced vesicular glutamate release in the CA3-hippocampal region as a consequence of diminished glutamate synthesis.

Effect of 17ß-estradiol on zinc content of hippocampal mossy fibers in ovariectomized adult rats.

Sex hormones such as estrogen (17ß-estradiol) may modulate the zinc content of the hippocampus during the female estrous cycle. The mossy fiber system is highly plastic in the adult brain and is influenced by multiple factors including learning, memory, and stress. However, whether 17ß-estradiol is able to modulate the morphological plasticity of the mossy fibers throughout the estrous cycle remains unknown. Ovariectomized (Ovx) female 70- to 90-day-old Sprague-Dawley rats without or with estrogen supplement (OvxE) were compared with control rats in three stages of the estrous cycle: diestrus, proestrus, and estrus. The brain tissue from each of the five groups was processed with Timm's silver sulfide technique using the Image J program to measure the mossy fiber area in the stratum lucidum of CA3. Total zinc in the hippocampus was measured using Graphite Furnace Atomic Absorption Spectrophotometry. Two additional (Ovx and OvxE) groups were examined in spatial learning and memory tasks using the Morris water maze. Similar increases in total zinc content and mossy fiber area were observed. The mossy fiber area decreased by 26 ± 2 % (difference ± SEM percentages) in Ovx and 23 ± 4 % in estrus as compared to the proestrus group and by 18 ± 2 % in Ovx compared to OvxE. Additionally, only the OvxE group learned and remembered the task. These results suggest that estradiol has a significant effect on zinc content in hippocampal CA3 during the proestrus stage of the estrous cycle and is associated with correct performance in learning and memory.

Hypertension secondary to abdominal mass.

Secondary arterial hypertension (HTN) can be caused by primary hyperaldosteronism, renovascular disease, sleep apnea syndrome, chronic kidney disease, drug use, etc. In addition, some urological disorders such as hydronephrosis can cause hypertension due to an increase in intraglomerular pressure that activates the renin angiotensin system.

A phase 2, double-blind, placebo-controlled trial of a valproate/lithium combination in ALS patients.

BACKGROUND: Few treatments are currently available for amyotrophic lateral sclerosis (ALS). A combination of lithium carbonate and valproic acid (VPA-Li) was shown to inhibit motor neuron death and delay disease progression. METHODS: Outpatients with a typical ALS presentation were enrolled in a randomized, placebo-controlled trial to assess the efficacy of orally administered VPA-Li. Changes in a functional scale score (ALSFRS-R) and survival rate were chosen as primary outcome variables. Secondary outcome variables included BMI, respiratory monitoring, quality of life, and a global impression of the treatment. RESULTS: Out of 42 patients enrolled, 20 individuals receiving VPA-Li and 18 on placebo treatment were included in the final analysis. Forty-five percent of patients receiving VPA-Li completed the trial, whereas only 22.22% of patients in the placebo group attended the final visit 18 months later (P = 0.09). Major changes in the ALSFRS-R score were observed, including a decrease of 1.195 points/month in the placebo group (95% CI: 0.7869-1.6031) and of 0.5085 under VPA-Li treatment (95% CI: 0.2288-0.7882) between months 6 and 14. Adverse events included bad mouth taste, constipation, and anorexia. Survival rate, body weight, and quality of life were positive outcomes by the end of the trial despite a high sample reduction, especially in the placebo group. The inclusion of 212 subjects in each group would confirm these differences. CONCLUSIONS: Combined VPA-Li treatment associated with slower ALS progression and better secondary outcomes. This dual treatment overcame the futility threshold and merits further investigation in ALS.