Creating models for the prediction of colostrum quantity, quality, and immunoglobulin G yield in multiparous Jersey cows from performance in the previous lactation and environmental changes.

With multiparous Jersey cows, colostrum production seems to be variable. Due to this, we aimed to identify specific variables involved in colostrum production and quality. From 2021 to 2023, data from 28 US farms (415 multiparous Jersey cows) were used to investigate if colostrum yield, IgG concentration (g/L), and IgG yield (g) could be predicted by farm variables and transmitting abilities. With the data collected, multiple regression equations were developed to aid in predicting colostrum yield, IgG concentration, and IgG yield. Colostrum was weighed and sampled for IgG analysis. Dairy Herd Information (DHI), calving, diet, and management information data were compiled. Days below 5°C (D<), days above 23°C (D>), and days between 5 and 23°C (D) were recorded. We evaluated transmitting abilities for milk, fat, protein, and dollars; previous lactation milk yield, fat percent, fat yield, protein percent, protein yield, previous lactation somatic cell score, previous lactation days open, previous lactation days dry, previous lactation days in milk, and previous parity; and current lactation parity, days dry, and calving information, birth ordinal day, and latitude. Colostrum yield, IgG yield, and concentration had 1 added to correct for values = 0. After addition, values >0 were transformed to ln or log10. Nontransformed variables were also used to develop the model. Variance inflation factor analysis was conducted, followed by backward elimination. The log10 colostrum yield model (R2 = 0.55; ß in parentheses) included herd size (-0.0001), ordinal days (-0.001), ln ordinal days (0.07), latitude (-0.02), dry period length (0.004), D< (-0.005), D (-0.003), time to harvest (0.05), ln time to harvest (-0.35), IgG (-0.004), log10 IgG (0.46), feedings per day (0.06), ln pasture access (-0.13), and ln previous lactation days open (0.14). The model showed that previous lactation days open contributed the most toward increasing and latitude contributed the most toward decreasing colostrum yield. The IgG model (R2 = 0.21) included herd size (0.02), D> (0.38), ln time to harvest (-19.42), colostrum yield (-4.29), ln diet type (18.00), ln previous lactation fat percent (74.43), and previous parity (5.72). The model showed that previous lactation milkfat percent contributed the most toward increasing and time from parturition to colostrum harvest contributed the most toward decreasing colostrum IgG concentration. The log10 IgG yield model (R2 = 0.79) included ln ordinal days (0.03), time to harvest (-0.01), colostrum yield (-0.11), ln colostrum yield (1.20), ln pasture access (-0.09), ln previous lactation fat percent (0.53), and previous parity (0.02). The model showed that colostrum yield contributed the most toward increasing IgG yield, followed by previous lactation milkfat percentage. Pasture access contributed the most toward decreasing IgG yield, although the contribution was very small. These models were validated using 39 samples from 22 farms. Actual minus predicted colostrum yield and IgG concentration and yield were 0.89 kg, -21.10 g/L, and -65.15 g, respectively. These models indicate that dry period management and cow information can predict colostrum yield and IgG concentration and yield.

Perspectives of dairy employees at the beginning of the COVID-19 pandemic: A survey of health risks and educational needs.

Our objective was to understand dairy employees' perceptions and educational needs at the onset of the COVID-19 pandemic. A bilingual (English and Spanish), anonymous survey targeted at dairy employees was circulated nationwide via university and allied industry media outlets. Responses (n = 63) from 11 states were received (May-Sep. 2020). Respondents worked in herds ranging from 50 to 40,000 animals in size. Dairy managers (33%) responded mostly to the English survey (52%), whereas entry-level workers (67%) chose the Spanish format (76%). Survey results highlighted different perspectives, educational needs, and preferred sources of information between English- and Spanish-speaking dairy workers. Overall, 83% of the respondents were somewhat concerned or very concerned about the COVID-19 pandemic. Respondents (51%) indicated that their main concern was "to bring the virus from work to home and make my family sick." Most dairy employees (83%) perceived that their employers were somewhat or very concerned about the pandemic. Respondents (65%) indicated that COVID-19 informative training was provided at the workplace, but training was more frequently undertaken among dairy managers (86%) than entry-level workers (53%). Most trainings (72%) were limited to posters on walls. The preferred means of information delivery was through in-person meetings at work (35%), with YouTube (29%) and on-demand videos (27%) as second and third options. The main source of information regarding the pandemic was social media (52%). Frequent handwashing (81%), limiting on-farm visits (70%), limiting agglomeration in break rooms (65%), hand sanitizer use (60%), and social distancing (60%) were the most common safety measures implemented at the workplace among the options given to respondents. Few respondents (38%) indicated that face-covering was required at work. Successful emergency plans on dairies should consider the outreach needs and preferences of dairy workers.

Perspective of dairy producers from California, Idaho, South Dakota, and Washington: Health and business implications of the COVID-19 pandemic during the second wave.

The aim of this study was to document California, Idaho, South Dakota, and Washington dairy producers' perspectives on the health and business implications of COVID-19 during the pandemic second wave. Dairy producers were reached by a 14-question anonymous mail survey during June and July of 2020. We obtained 226 responses (response rate: 9.3% CA, 8.6% ID, 31.4%, and 10.0% WA). Responses were grouped by state (CA: 48.7%, ID: 15.9%, SD: 21.7%, or WA: 13.7%) and dairy size [based on number of cows; small (<100): 14.1%, medium (100-499): 27.7%, medium-large (500-1,999): 33.2%, or large (≥2,000): 25.0%]. Survey responses were summarized, and multiple correspondence analysis was used to map responses and identify data clusters. At the time of the survey, some respondents suspected (3%) or had confirmed (9%) COVID-19 cases on their premises. Respondents were somewhat or very concerned about the health (75%) and business (92%) implications associated with COVID-19. Producers were concerned about the health of their families, employees, and employees' families; having to reduce production; workforce shortage; limited goods availability; and lack of services. Producers perceived that their employees were somewhat or very concerned (74%) with the pandemic. There was COVID-19 safety information or training provided (78%) or intended (4%) in English (22%), Spanish (23%), or both (55%). The focus of training was as follows: how to remain healthy at work (91%) and at home (60%), what to do if a worker gets sick (77%), and sick leave information (54%). Nevertheless, 18% of the respondents answered that training was not going to be provided. The following control measures implemented: providing hand sanitizer or disinfectant wipes (78%), instruction on frequent hand-washing (76%), social distancing (59%), prevention of employee gatherings (54%), providing and requiring the use of face masks (49%), and limiting on-farm visitors (44%). Multiple correspondence analysis showed that concern with health risk and business impact of the COVID-19 pandemic, as well as mitigation and response strategies implemented, varied based on respondent's dairy size and state. The greatest concerns were reported by producers from California and large and medium-large dairies, whereas the fewest concerns were reported by producers from small dairies. Results from this survey highlighted the health and business concerns of dairy producers from California, Idaho, South Dakota, and Washington during the COVID-19 pandemic and the mitigation efforts adopted. In conclusion, mitigation measures were adopted by most dairy producers but in various degrees. Dairy industry service providers and educators were secondary educational resources during the pandemic; thus, future efforts toward centralized access to dairy specific bilingual educational materials are suggested.

Stroke symptoms impact on mental and physical health: A Lebanese population based study.

BACKGROUND/OBJECTIVE: Stroke symptoms in the absence of diagnosed stroke are common worldwide and associated with stroke risk factors and great impact on the physical and mental health functioning. The aim of this study was to assess, at the national level, the association of stroke symptoms with mental and physical health. METHODS: Quality of life was assessed using physical and mental component summary scores (PCS and MCS) of the Short Form 12v2 Health Survey in the Lebanese population. We assessed the differences in the mean PCS and MCS scores among asymptomatic individuals with no stroke/transient ischemic attack (TIA) history (n=1167), symptomatic individuals with no stroke/TIA history (n=125) and those with stroke/TIA history (n=46). Psychometric properties of the Lebanese version of the SF- 12v2 were evaluated using principal component analysis. RESULTS: Symptomatic individuals had an average PCS scores of 2.31 (95%CI: 0.75-3.88) points lower and those with stroke/TIA history had 3.26 (95%CI: 1.01-5.51) points lower when compared with asymptomatic individuals with no stroke/TIA history. Similarly, MCS scores for symptomatic individuals were 2.58 (95%CI: 1.02-4.13) points lower and those with stroke/TIA history had 3.28 (95%CI: 1.06-5.50) points lower than asymptomatic individuals. CONCLUSION: Physical and mental health functioning declined among symptomatic individuals and those with stroke/TIA history. Thus, frequent monitoring for the early detection of stroke symptoms may be recommended.

First Lebanese Antibiotic Awareness Week campaign: knowledge, attitudes and practices towards antibiotics.

Antibiotic resistance (ABR) is a major global health threat that increases the risk of treatment failure and increases medical costs. One of the most common factors contributing to the spread of ABR is self-medication. The public, as well as workers in clinical and veterinary sectors, commit false practices towards appropriate antibiotic use, favouring the spread of resistance. As such, the first Lebanese Antibiotic Awareness Week campaign was initiated with a human-centred and interactive approach. The data showed a strikingly low level of antibiotic awareness. Cooperation between relevant stakeholders, policy-makers and health actors is crucial to control and overcome the problem of ABR.

Mechanisms of Drug Binding to Voltage-Gated Sodium Channels.

Voltage-gated sodium (Na+) channels are expressed in virtually all electrically excitable tissues and are essential for muscle contraction and the conduction of impulses within the peripheral and central nervous systems. Genetic disorders that disrupt the function of these channels produce an array of Na+ channelopathies resulting in neuronal impairment, chronic pain, neuromuscular pathologies, and cardiac arrhythmias. Because of their importance to the conduction of electrical signals, Na+ channels are the target of a wide variety of local anesthetic, antiarrhythmic, anticonvulsant, and antidepressant drugs. The voltage-gated family of Na+ channels is composed of α-subunits that encode for the voltage sensor domains and the Na+-selective permeation pore. In vivo, Na+ channel α-subunits are associated with one or more accessory ß-subunits (ß1-ß4) that regulate gating properties, trafficking, and cell-surface expression of the channels. The permeation pore of Na+ channels is divided in two parts: the outer mouth of the pore is the site of the ion selectivity filter, while the inner cytoplasmic pore serves as the channel activation gate. The cytoplasmic lining of the permeation pore is formed by the S6 segments that include highly conserved aromatic amino acids important for drug binding. These residues are believed to undergo voltage-dependent conformational changes that alter drug binding as the channels cycle through the closed, open, and inactivated states. The purpose of this chapter is to broadly review the mechanisms of Na+ channel gating and the models used to describe drug binding and Na+ channel inhibition.

Honeybee locomotion is impaired by Am-CaV3 low voltage-activated Ca2+ channel antagonist.

Voltage-gated Ca2+ channels are key transducers of cellular excitability and participate in several crucial physiological responses. In vertebrates, 10 Ca2+ channel genes, grouped in 3 families (CaV1, CaV2 and CaV3), have been described and characterized. Insects possess only one member of each family. These genes have been isolated in a limited number of species and very few have been characterized although, in addition to their crucial role, they may represent a collateral target for neurotoxic insecticides. We have isolated the 3 genes coding for the 3 Ca2+ channels expressed in Apis mellifera. This work provides the first detailed characterization of the honeybee T-type CaV3 Ca2+ channel and demonstrates the low toxicity of inhibiting this channel. Comparing Ca2+ currents recorded in bee neurons and myocytes with Ca2+ currents recorded in Xenopus oocytes expressing the honeybee CaV3 gene suggests native expression in bee muscle cells only. High-voltage activated Ca2+ channels could be recorded in the somata of different cultured bee neurons. These functional data were confirmed by in situ hybridization, immunolocalization and in vivo analysis of the effects of a CaV3 inhibitor. The biophysical and pharmacological characterization and the tissue distribution of CaV3 suggest a role in honeybee muscle function.

Effects of dietary betaine on milk yield and milk composition of mid-lactation Holstein dairy cows.

Betaine, naturally found in plants and an oxidative product of choline, is converted to acetate in the rumen, which may be used for milk fat synthesis. The objective of this study was to determine the effect of supplemental dietary betaine on milk yield and milk composition. Eighteen Holstein dairy cows (126±5 d in milk; mean ± SD) were randomly assigned to a sequence of treatments of rumen-unprotected betaine at 0, 25, 50, and 100 g/d added to a standard lactation ration in a 4×4 Latin square design. Animals were fed individually with feed intake and milk yield recorded daily. Body condition score and body weight were recorded on the last day of each period that lasted 16 d, with milk sampled on the last 2 d of each period. Milk composition was determined by a Dairy Herd Improvement Association laboratory and milk fatty acids were determined by gas chromatography. Data collected over the last 2 to 3 d were analyzed using the MIXED procedure in SAS (SAS Institute Inc., Cary, NC). Milk yield (mean ± SEM) was increased by betaine when fed at 100g/d (22.4, 22.5, 22.8, 24.1±1.19 kg/d for 0, 25, 50, and 100g of betaine/d, respectively). No effect of dietary betaine was detected on dry matter intake, feed efficiency, body weight, or body condition score. Percentages of milk fat, lactose, solids-not-fat, and somatic cell count were not altered; however, protein concentration was decreased by betaine supplementation as compared with the control (3.35, 3.28, 3.27, and 3.28±0.07% for 0, 25, 50, and 100 g of betaine/d, respectively). Daily yields of milk protein, fat, lactose, energy-corrected milk, and 3.5% fat-corrected milk did not differ with betaine supplementation. Overall, inclusion of dietary betaine at 100 g/d increased milk yield, whereas all levels of betaine supplementation decreased milk protein percent and slightly altered milk fatty acid profile. Further studies are needed to determine the ruminal fermentation characteristics and the optimum rate of supplemental betaine for dairy cows.

Molecular analysis of imipenem-resistant Acinetobacter baumannii isolated from US service members wounded in Iraq, 2003-2008.

Global dissemination of imipenem-resistant (IR) clones of Acinetobacter baumannii - A. calcoaceticus complex (ABC) have been frequently reported but the molecular epidemiological features of IR-ABC in military treatment facilities (MTFs) have not been described. We characterized 46 IR-ABC strains from a dataset of 298 ABC isolates collected from US service members hospitalized in different US MTFs domestically and overseas during 2003-2008. All IR strains carried the bla(OXA-51) gene and 40 also carried bla(OXA-23) on plasmids and/or chromosome; one carried bla(OXA-58) and four contained ISAbal located upstream of bla(OXA-51). Strains tended to cluster by pulsed-field gel electrophoresis profiles in time and location. Strains from two major clusters were identified as international clone I by multilocus sequence typing.

Methicillin-resistant Staphylococcus aureus infection in combat support hospitals in three regions of Iraq.

SUMMARYStaphylococcus aureus is a leading cause of infections in deployed service members. Based on a molecular epidemiological study of 182 MRSA isolates from patients in three U.S. Army combat support hospitals in separate regions in Iraq, USA300 clone was the most predominant (80%) pulsotype. This finding suggested that strain carriage from the home country by military personnel is epidemiologically more important than local acquisition.

Bioavailability of alpha-linolenic acid from flaxseed diets as a function of the age of the subject.

BACKGROUND: Dietary flaxseed may have beneficial cardiovascular effects. An aged population has a higher incidence of cardiovascular disease, but they may react differently to flaxseed in the diet. OBJECTIVE: To investigate the response, over a period of 4 weeks, of subjects aged 18-29 or 45-69 years to a diet containing the same amount of alpha-linolenic acid (ALA) (6 g) introduced in the form of ground flaxseed (30 g) or flaxseed oil. RESULTS: All subjects who received flaxseed oil showed a significant increase in plasma ALA and eicosapentaenoic acid (EPA) concentrations over the course of this study. Subjects who received ground flaxseed in the 18-29-year-old group showed a statistically significant increase in their plasma ALA levels, and although there was a trend in the same direction for the 45-69-year-old subjects, this did not achieve statistical significance. The diets induced no major changes in platelet aggregation, plasma total cholesterol, low-density lipoprotein or high-density lipoprotein cholesterol levels in any of the groups. Younger subjects showed a decrease in triglyceride (TG) values compared with older subjects. There were no significant side effects that caused compliancy issues. CONCLUSION: Subject age does not seem to be a major determining factor in influencing ALA absorption from a flaxseed-supplemented diet nor in the metabolism of ALA to EPA in the groups fed flaxseed oil. Concerns about side effects in older subjects administered a higher fiber load in a flaxseed-supplemented diet are not justified. However, younger but not older subjects showed a beneficial decrease in circulating TGs due to flaxseed supplementation.

Effect of preslaughter feeding and ractopamine hydrochloride supplementation on growth performance, carcass characteristics, and end product quality in market dairy cows.

An experiment was conducted in market dairy cows to determine the effect of feeding time and ractopamine hydrochloride (RAC) on growth performance, carcass characteristics, and end product quality. In 3 replicates, 9 Holstein cows per replicate (n = 27; 659 +/- 25.3 kg initial BW) culled from 3 dairies were randomly assigned to 3 treatments: 1) slaughter immediately (control), 2) feed for 90 d (NoR), or 3) feed for 90 d with RAC (312 mg.cow(-1).d(-1)) for the final 32 d (RAC). On d 0, NoR and RAC cows were placed in individual pens and fed a high concentrate diet (86% concentrate, DM basis) for 90 d before slaughter. All cows were subjectively scored for BCS and locomotion score on d 0, and NoR and RAC cows were evaluated again after 90 d. Individual DMI was recorded daily throughout the trial, and BW was collected every 14 d. Age and age x treatment did not affect (P > 0.05) any of the traits evaluated in this study. When cows fed for 90 d (NoR and RAC combined) were compared with nonfed controls, fed cows had greater (P < 0.001) final BCS, BW and HCW, lower (P < 0.001) final locomotion score, and greater (P < 0.03) dressing percentage, external fat thickness, and marbling score. Fed cows also tended to have more desirable yield grade (P = 0.08), ribeye area (P = 0.11), fat color (P = 0.09), lean maturity (P = 0.06), and quality grade (P = 0.09) compared with control cows. Warner-Bratzler shear force was not affected (P = 0.23) by feeding. However, a 12-member trained sensory panel revealed that fed cow carcasses had more desirable (P < 0.04) tenderness, juiciness, and overall acceptability than control cow carcasses. Flavor intensity also tended (P = 0.10) to be more desirable for fed vs. control cows. No difference (P > 0.10) in off-flavor was detected among treatments. Finally, there was no effect (P > 0.10) of RAC on growth performance, carcass characteristics, or end product quality. In conclusion, feeding a high concentrate diet for 90 d improved important live animal, carcass, and end product characteristics related to the quality and palatability of beef from market dairy cows; however, no effect of RAC supplementation was observed.

Assessment of management and basic beef quality assurance practices on Idaho dairies.

In 2004 a mail-in survey was conducted to establish a baseline level of awareness and knowledge related to dairy beef quality assurance (BQA) issues in Idaho. A 30-question survey was mailed to every (n = 736) registered Idaho dairy. Two-hundred seventy-three (37%) dairies participated and were categorized as small (n <201 cows; 53.5%), medium-sized (n = 201 to 1,000 cows; 27.1%) or large (n >1,000 cows; 19.4%). The majority of respondents were dairy owners (83%). Eighty-nine percent of respondents indicated they followed BQA recommendations for animal care. The neck region in cows was used by 68% of respondents for i.m. injections and by 80% for s.c. injections. In calves, the values were 61 and 78%, respectively. Seventy-four percent of respondents indicated they had been trained for injections. Training methods cited included veterinarians (19.8%), dairy owners (16.8%), experience (9.9%), and BQA events or schools (4.5%). The importance of BQA in the dairy industry was rated 2.6 on a 5-point scale (0 = low; 4 = high). Participants rated the effect of dairy animals on the beef industry at 2.5. Plastic ear tags were the preferred method of animal identification, with 100% of large dairies, 97.3% of medium-sized dairies, and 84% of small dairies citing their use. Less than 10% used electronic identification for their animals. Almost half (48%) of large and medium-sized (49%) dairies and 32% of small dairies supported a national animal identification program. A mandatory identification program was supported by 41, 69, and 59% for small, medium-sized, and large dairies, respectively. The percentage of dairies keeping records was similar between small (93%), medium-sized (99%), and large (100%) dairies. Most small dairies (58%) used some form of paper records, whereas most medium-sized (85%) and large (100%) dairies used computers for record keeping. The preferred method to market cull cows by Idaho dairies was the auction market (64%), followed by order buyers (17%), direct to the packer (17%), private treaty sales (16%), and forward contracts (1%). To market calves, dairies used private treaty sales (52%), auction markets (42%), order buyers (14%), and forward contracts (1%). The results of this study will be used by University of Idaho Extension faculty in the design, development, and delivery of dairy BQA program information and materials.

Protein kinase C activation inhibits alpha1D L-type Ca channel: a single-channel analysis.

The recently reported alpha1D Ca channel in the heart is known to be regulated by protein kinase C (PKC) at the whole cell level and has been implicated in atrial fibrillation. The biophysical basis of this regulation at the single-channel level is not known. Therefore, the effect of PKC activation was studied on alpha1D Ca channel expressed in tsA201 cells using cell-attached configuration. Unitary currents were recorded in the presence of 70 mM Ba2+ as the charge carrier at room temperature. Under basal condition, channel activity was rare and infrequent; however, Bay K 8644 (1 microM) induced channel openings with a conductance of 22.3 pS. Single channel analysis of open and closed time distributions were best fitted with a single exponential. PKC activation by 4alpha-phorbol 12-myristate 13-acetate (PMA; 10 nM), a phorbol ester derivative, resulted in a decrease in open probability and increase in closed-time without any significant effect on the conductance of the alpha1D Ca channel. This is consistent with a decreased entry of alpha1D Ca channel into open states in the presence of PMA. PMA effects could not be reproduced by 4-alpha Phorbol, an inactive PMA analogue. These data show, for the first time, (1) the alpha1D Ca channel activity at the single-channel level and (2) the biophysical basis by which PKC activation inhibits the alpha1D Ca channel. The shortening of the open-time and the lengthening of the closed-time constants and the increase in blank sweeps may explain the inhibition of the previously reported whole-cell alpha1D Ca current. Altogether, these data are essential for understanding the complex role of alpha1D Ca channel not only in physiological settings but also in pathological settings such as atrial fibrillation.

Changes in action potentials and intracellular ionic homeostasis in a ventricular cell model related to a persistent sodium current in SCN5A mutations underlying LQT3.

In LQT3 patients, SCN5A mutations induce ultraslow inactivation of a small fraction of the hNav1.5 current, i.e. persistent Na+ current (IpNa). We explored the time course of effects of such a change on the intracellular ionic homeostasis in a model of guinea-pig cardiac ventricular cell [Pasek, M., Simurda, J., Orchard, C.H., Christé, G., 2007b. A model of the guinea-pig ventricular cardiomyocyte incorporating a transverse-axial tubular system. Prog. Biophys. Mol. Biol., this issue]. Sudden addition of IpNa prevented action potential (AP) repolarization when its conductance (gpNa) exceeded 0.12% of the maximal conductance of fast INa (gNa). With gpNa at 0.1% gNa, the AP duration at 90% repolarization (APD90) was initially lengthened to 2.6-fold that in control. Under regular stimulation at 1 Hz it shortened progressively to 1.37-fold control APD90, and intracellular [Na+]i increased by 6% with a time constant of 106 s. Further increasing gpNa to 0.2% gNa caused an immediate increase in APD90 to 5.7-fold that in control, which decreased to 2.2-fold that in control in 30s stimulation at 1 Hz. At this time diastolic [Na+]i and [Ca2+]i were, respectively, 34% and 52% higher than in control and spontaneous erratic SR Ca release occurred. In the presence of IpNa causing 46% lengthening of APD90, the model cell displayed arrhythmogenic behaviour when external [K+] was lowered to 5 mM from an initial value at 5.4 mM. By contrast, when K+ currents IKr and IKs were lowered in the model cell to produce the same lengthening of APD90, no proarrhythmic behaviour was observed, even when external [K+] was lowered to 2.5 mM.

Effect of dietary hempseed intake on cardiac ischemia-reperfusion injury.

Polyunsaturated fatty acids (PUFAs) have significant, cardioprotective effects against ischemia. Hempseed contains a high proportion of the PUFAs linoleic acid (LA) and alpha-linolenic acid (ALA), which may have opposing effects on postischemic heart performance. There are no reported data concerning the cardiovascular effects of dietary hempseed intake. A group of 40 male Sprague-Dawley rats were distributed evenly into four groups that were fed for 12 wk a normal rat chow supplemented with hempseed (5% and 10%), palm oil (1%), or a 10% partially delipidated hempseed that served as a control. Plasma ALA and gamma-linolenic acid levels were significantly elevated in the rats that were fed a 5% or 10% hempseed-supplemented diet, but in heart tissue only ALA levels were significantly elevated in the rats fed these diets compared with control. After the dietary interventions were completed, postischemic heart performance was evaluated by measuring developed tension, resting tension, the rates of tension development and relaxation, and the number of extrasystoles. Hearts from rats fed a hempseed-supplemented diet exhibited significantly better postischemic recovery of maximal contractile function and enhanced rates of tension development and relaxation during reperfusion than hearts from the other groups. These hearts, however, were not protected from the occurrence of extrasystoles, nor were the increases in resting tension altered during ischemia or reperfusion as a function of any dietary intervention. Our data demonstrate that dietary hempseed can provide significant cardioprotective effects during postischemic reperfusion. This appears to be due to its highly enriched PUFA content.

Clinical aspects and physiopathology of Brugada syndrome: review of current concepts.

Brugada syndrome (BS) is an inherited cardiac disorder characterized by typical electrocardiographic patterns of ST segment elevation in the precordial leads, right bundle branch block, fast polymorphic ventricular tachycardia in patients without any structural heart disease, and a high risk of sudden cardiac death. The incidence of BS is high in male vs. female (i.e., 8-10/1: male/female). The disorder is caused by mutations in the SCN5A gene encoding Nav1.5, the cardiac sodium channel, which is the only gene in which mutations were found to cause the disease. Mutations in SCN5A associated with the BS phenotype usually result in a loss of channel function by a reduction in Na+ currents. We review the clinical aspects, risk stratification, and therapeutic management of this important syndrome.

Differential modulation of Nav1.7 and Nav1.8 peripheral nerve sodium channels by the local anesthetic lidocaine.

1 Voltage-gated Na+ channels are transmembrane proteins that are essential for the propagation of action potentials in excitable cells. Nav1.7 and Nav1.8 dorsal root ganglion Na+ channels exhibit different kinetics and sensitivities to tetrodotoxin (TTX). We investigated the properties of both channels in the presence of lidocaine, a local anesthetic (LA) and class I anti-arrhythmic drug. 2 Nav1.7 and Nav1.8 Na+ channels were coexpressed with the beta1-subunit in Xenopus oocytes. Na+ currents were recorded using the two-microelectrode voltage-clamp technique. 3 Dose-response curves for both channels had different EC50 (dose producing 50% maximum current inhibition) (450 microm for Nav1.7 and 104 microm for Nav1.8). Lidocaine enhanced current decrease in a frequency-dependent manner. Steady-state inactivation of both channels was also affected by lidocaine, Nav1.7 being the most sensitive. Only the steady-state activation of Nav1.8 was affected while the entry of both channels into slow inactivation was affected by lidocaine, Nav1.8 being affected to a larger degree. 4 Although the channels share homology at DIV S6, the LA binding site, they differ in their sensitivity to lidocaine. Recent studies suggest that other residues on DI and DII known to influence lidocaine binding may explain the differences in affinities between Nav1.7 and Nav1.8 Na+ channels. 5 Understanding the properties of these channels and their pharmacology is of critical importance to developing drugs and finding effective therapies to treat chronic pain.

Role of arginine residues on the S4 segment of the Bacillus halodurans Na+ channel in voltage-sensing.

The one-domain voltage-gated sodium channel of Bacillus halodurans (NaChBac) is composed of six transmembrane segments (S1-S6) comprising a pore-forming region flanked by segments S5 and S6 and a voltage-sensing element composed of segment S4. To investigate the role of the S4 segment in NaChBac channel activation, we used the cysteine mutagenesis approach where the positive charges of single and multiple arginine (R) residues of the S4 segment were replaced by the neutrally charged amino acid cysteine (C). To determine whether it was the arginine residue itself or its positive charge that was involved in channel activation, arginine to lysine (R to K) mutations were constructed. Wild-type (WT) and mutant NaChBac channels were expressed in tsA201 cells and Na+ currents were recorded using the whole-cell configuration of the patch-clamp technique. The current/voltage (I-V) and conductance/voltage (G-V) relationships steady-state inactivation (h(infinity)) and recovery from inactivation were evaluated to determine the effects of the S4 mutations on the biophysical properties of the NaChBac channel. R to C on the S4 segment resulted in a slowing of both activation and inactivation kinetics. Charge neutralization of arginine residues mostly resulted in a shift toward more positive potentials of G-V and h(infinity) curves. The G-V curve shifts were associated with a decrease in slope, which may reflect a decrease in the gating charge involved in channel activation. Single neutralization of R114, R117, or R120 by C resulted in a very slow recovery from inactivation. Double neutralization of R111 and R129 confirmed the role of R111 in activation and suggested that R129 is most probably not part of the voltage sensor. Most of the R to K mutants retained WT-like current kinetics but exhibited an intermediate G-V curve, a steady-state inactivation shifted to more hyperpolarized potentials, and intermediate time constants of recovery from inactivation. This indicates that R, at several positions, plays an important role in channel activation. The data are consistent with the notion that the S4 is most probably the voltage sensor of the NaChBac channel and that both positive charges and the nature of the arginine residues are essential for channel activation.