Pharmacological Protocols Research Articles

Effect of thiamine pyrophosphate on the characteristics of farrowing and piglet vitality

Asphyxia is considered the main non-infectious cause of prepartum mortality in swine, as well as an important factor that negatively affects neonatal vitality and can trigger physiological and metabolic disorders. Hence, the search for pharmacological protocols to reduce the harmful effects of asphyxia is a key area of research. Recent observations show that administering thiamine pyrophosphate (TPP) prior to a hypoxic event in certain species (rabbits, rats) has a neuroprotector effect that preserves energy metabolism under hypoxic conditions. Given this, the objective of this study was to evaluate a prophylactic protocol in high- and low-vitality neonate piglets based on TPP's effect on physiological and metabolic responses, body temperature, and weight. A total of 149 piglets born from 15 multiparous sows were used. The dams were randomly divided into two groups: control (NaCl 0.9%) and TPP (25 ml of TTP) administered 24 and 12 h before the expected farrowing date. The following reproductive variables of the sows were recorded: duration of farrowing, total number of piglets born per litter, number of liveborn piglets per litter, number of stillbirths and mummified fetuses at birth, and number of live piglets at weaning. In addition, the expulsion interval and vitality of all neonates were evaluated, body temperatures were recorded at ten intervals, and physiological profiles (blood gases, electrolytes, glucose) were registered for each neonate. Results show that the TPP-treated sows had shorter farrowing duration (P = 0.0060) and higher percentage of high-vitality neonates (60%). Moreover, their offspring exhibited greater vitality, fewer imbalances in their physiological and metabolic profiles, and greater weight gain at weaning (P < 0.0001). Findings suggest that administering TPP exerts a protective effect when hypoxic events occur, though this differs from results obtained with rat pups, where applying TPP after such events did not provide protection from asphyxia-induced damage. These differences may be due to the moment at which TPP was applied. The application time we selected was distinct from the procedure followed with rats because it was based on a dataset that describes the influence of administering TPP as a prophylactic treatment before a hypoxic event. Prophylactic administration of TPP to sows at the end of gestation exerted a neuroprotective effect on neonatal vitality and gas exchanges and energy metabolism in the offspring that were reflected in the greater weekly weight gain in those piglets.

Compliance With Guidelines of Hypertension Management, and Associated Factors Among the Health Practitioners.

The consequences of uncontrolled hypertension such as stroke, myocardial infarction, retinal damage and others are significantly affecting individual and the community in large. The patients are suffering from compromised quality of life, permanent disability, and premature death in developing countries. The reason for the existence of the gap hasn't been clear yet. An institutional-based retrospective cross-sectional study designed from patient medical record data was used to assess compliance with the federal democratic and republic of Ethiopia ministry of health hypertension management guideline. Medical records of adult Patients treated for hypertension from March 2019 to March 2020 were reviewed. Systematic sampling technique from patients' medical records every 10th interval was taken to reach the total sample size. The collected data were checked for completeness, consistency, and accuracy before analysis. Data were coded, entered, and cleaned using Epi-data 7 and exported to SPSS version 25 for analysis. Overall compliance with the hypertension guideline was found to be poor; only 75 (19.5%) patients managed according to the guideline in these institutions. The majority of health practitioners complied with the pharmacological Antihypertensive treatment protocols for 238 (62.0%) patients, while for 146 (38.0%) of the patients the guideline was not followed. Combining the lifestyle modification recommendations and pharmacological antihypertensive treatment to assess compliance with the hypertension management guideline, only 75 (19.5%) patients managed as per the guideline, while 309 (80.5%) did not. Nearly more than two-thirds of the patients were not managed following the national hypertension guideline, and health practitioners are failed to recommend lifestyle modifications for most of the patients, as a result, the majority of the hypertensive patients are being exposed to complications and urgent intervention is demanded against the gap.

Pain management in periodontal therapy using local anesthetics and other drugs: an integrative review.

Surgical and non-surgical periodontal procedures often lead to postoperative pain. Clinicians use pharmacological methods such as anesthetics, anti-inflammatory drugs, and analgesics for relief. However, the multitude of options makes it challenging to select the best approach for routine dental care. This review aimed to describe previous studies regarding the pharmacological management used for pain control during periodontal procedures as well as factors that may interfere with patients' perception of pain. We included studies (period of 2000-2023, whose approach corresponded to the pharmacological protocols used for preoperative, trans-operative, and postoperative pain control in adult patients undergoing surgical and non-surgical periodontal therapy. A total of 32 studies were included in the analysis, of which 17 (53%) were related to anesthetic methods and 15 (47%) were related to therapeutic protocols (anti-inflammatory/analgesic agents). These studies predominantly involved nonsurgical periodontal procedures. Studies have reported that factors related to age, type of procedure, and anxiety can influence pain perception; however, only seven of these studies evaluated anxiety. Numerous methods for pain control can be applied in periodontal therapy, which are accomplished through anesthetic methods and/or therapeutic protocols. Factors such as anxiety, age, and type of procedure are related to pain perception in patients. Thus, it is the responsibility of dentists to evaluate each clinical situation and define the best protocol to follow based on the literature.

Change of pulmonary function tests in hospitalized COVID-19 patients at third and sixth month follow-up.

The effect of COVID-19 infection on pulmonary function is unknown. This study aimed to evaluate pulmonary function tests (PFTs) of patients hospitalized with the diagnosis of COVID-19 pneumonia at 3 and 6 months post-discharge. Patients aged 18 years and over who had positive COVID-19 PCR test results and were hospitalized in the pandemic service between 1 May 2020 and 31 October 2020, were included in the study. All patients were evaluated with PFTs FVC, FEV1, FEV1/FVC, and FEF25-75 at 3 and 6 months after discharge. The mean age of 34 patients included in the study was 47.7 ± 12.7 years. The FVC, FEV1, FEV1/FVC, and FEF25-75 measurements at 3 and 6 months post-discharge showed no significant difference (P = 0.765, P = 0.907, P = 0.707, and P = 0.674, respectively). There was no significant difference in any PFT measurements at the third month follow-up, regardless of the pharmacological treatment protocols applied during hospitalization (P > 0.05). However, FEV1/FVC and FEF25-75 levels were 83.1 [3.4]% and 91.0 [10.0]%, respectively, in those who received systemic steroid treatment, and 78.3 ± 8.5% and 72.5 ± 25.7% in those who did not (P = 0.019 and P = 0.048, respectively). In addition, FVC and FEV1 levels increased significantly from the third to the sixth month follow-up in patients who received systemic steroid therapy (P = 0.035 and P = 0.018, respectively). Although there is no significant difference in PFT measurements from 3 to 6 months in COVID-19 patients, systemic steroid therapy may have a beneficial effect on respiratory function in COVID-19 patients.

Bradykinin and Galectin-3 in Survived and Deceased Patients with COVID-19 Pneumonia: An Increasingly Promising Biochemical Target.

There are still no definite curative or preventive strategies for COVID-19 disease. It is crucial to fully comprehend the pathogenesis of COVID-19 infection so that we can develop expedient pharmacological protocols. While the impact of cytokine storm on COVID-19 severity has been one of the most tested hypotheses, the role of bradykinin and various other oxidative stress markers has been relatively under-researched. Their levels can be determined immediately after a hospital admission so they could be used as early predictors of the further development of the disease. The study aims at evaluating the possibility of using bradykinin and galectin-3 levels as early predictors that COVID-19 disease will progress into a severe case. Material and methods. The study was conducted as a prospective cross-sectional study. It included 47 consecutive adult patients with confirmed SARS-CoV-2 infection and COVID-19 pneumonia. All study subjects were admitted for a hospital treatment to the tertiary Clinical Hospital Center Bezanijska kosa, Belgrade, Serbia on June 2021. The blood samples were collected at the patients' admission. The analyses of demographic, radiological, and clinical data were later conducted for both groups (the deceased patients and those who survived). In addition, we analyzed the potential relations between the outcome and the levels of bradykinin and galectin-3 measured immediately after the patients were admitted to the hospital. The patients who passed away were predominantly older men with comorbidities. We recorded higher CT scores in the deceased patients and the significantly higher levels of urea, creatinine, CK, troponine, CRP, and other laboratory markers. They stayed at the ICU unit longer and required mechanical ventilation more frequently than the patients who survived. On the other hand, no differences were recorded in the time periods passing from the onset of the systems to the hospital admissions. Finally, we can highlight several independent predictors of mortality in patients with COVID-19 pneumonia, including the following: (1) patients who are 50 or more years old, (2) with in-hospital stays are longer that 4 days, (3) bradykinin levels surpass 220000 pg/ml, (4) D-dimer, creatinine, and CRP are elevated, and (5) comorbidities were present (such as hypertension and diabetes). The present study strongly supports the bradykinin storm hypothesis. Since elevated bradykinin levels have been found in most COVID-19 cases with fatal outcomes, the future therapeutical strategies for COVID-19 have to be focused on reducing bradykinin serum concentrations.

Assessing costs of a hypertension program in primary care: evidence from the HEARTS program in Mexico.

ABSTRACTObjective.In 2021, Mexico launched the HEARTS program to improve the prevention and control of cardiovascular disease (CVD) risk factors in 20 primary care facilities in the states of Chiapas and Yucatán. This study projects the annual cost of program implementation and discusses budgetary implications for scaling up the program.Methods.We obtained district-level data on treatment protocols, medication costs, and other resources required to prevent and treat CVD. We used the HEARTS Costing Tool to estimate total and per-patient costs. A “partial implementation” scenario calculated the costs of implementing HEARTS if existing pharmacological treatment protocols are left in place. The second scenario, “full implementation,” examined costs if programs use HEARTS pharmacological protocol.Results.Respectively in the partial and full implementation scenarios, total annual costs to implement and operate HEARTS were $260 023 ($32.1 per patient/year) and $255 046 ($31.5 per patient/year) in Chiapas, and $1 000 059 ($41.3 per patient/year) and $1 013 835 ($43.3 per patient/year) in Yucatán. In Chiapas, adopting HEARTS standardized treatment protocols resulted in a 9.7 % reduction in annual medication expenditures relative to maintaining status-quo treatment approaches. In Yucatán, adoption was $12 875 more expensive, in part because HEARTS hypertension treatment regimens were more intensive than status quo regimens.Conclusion.HEARTS in the Americas offers a standardized strategy to treating and controlling CVD risk factors. In Mexico, approaches that may lead to improved program affordability include adoption of the recommended HEARTS treatment protocols with preferred medications and task shifting of services from physicians to nurses and other providers.

Role of dihydropyridine calcium channel blockers in coronary bypass surgery using the radial artery graft

Aim. To assess the effect of a pharmacological protocol for the prevention of radial artery spasm, which is based on the systemic and local use of dihydropyridine calcium channel blockers, on the long-term outcomes of autoarterial coronary artery bypass grafting.Material and methods. According to the protocol, oral nifedipine at a dose of 5 mg/day is prescribed 3 days before surgery. Then, after the radial artery is isolated, the vessel is preserved in a solution of nifedipine (adalat) until it is used. After releasing the clamp from the aorta, a nifedipine (adalat) is infused intravenously at a dose of 0,63 mg/h. In the postoperative period, the infusion of nifedipine continues for 6 hours. In the future, patients are recommended to take dihydropyridine calcium channel blockers at a dose of 5 mg/day after discharge from the hospital.Results. The use of the pharmacological protocol (n=225) is associated with a lower number of major cardiovascular events (mortality, myocardial infarction, stroke) compared with the control group (n=230) (9,3% and 15,7%, p=0,031) during the 5-year follow-up. This result was achieved mainly by reducing the incidence of myocardial infarction (6,2% and 12,6%, p=0,018). Also, the use of the pharmacological protocol led to a decrease in repeated revascularizations (4,4% and 16,1%, p=0,0001) compared with the control group.Conclusion. The use of a pharmacological protocol for the prevention of radial artery spasm based on the systemic use of dihydropyridine calcium channel blockers improves the long-term outcomes of autoarterial coronary artery bypass grafting.

Noradrenaline and Movement Initiation Disorders in Parkinson's Disease: A Pharmacological Functional MRI Study with Clonidine.

Slowness of movement initiation is a cardinal motor feature of Parkinson’s disease (PD) and is not fully reverted by current dopaminergic treatments. This trouble could be due to the dysfunction of executive processes and, in particular, of inhibitory control of response initiation, a function possibly associated with the noradrenergic (NA) system. The implication of NA in the network supporting proactive inhibition remains to be elucidated using pharmacological protocols. For that purpose, we administered 150 μg of clonidine to 15 healthy subjects and 12 parkinsonian patients in a double-blind, randomized, placebo-controlled design. Proactive inhibition was assessed by means of a Go/noGo task, while pre-stimulus brain activity was measured by event-related functional MRI. Acute reduction in noradrenergic transmission induced by clonidine enhanced difficulties initiating movements reflected by an increase in omission errors and modulated the activity of the anterior node of the proactive inhibitory network (dorsomedial prefrontal and anterior cingulate cortices) in PD patients. We conclude that NA contributes to movement initiation by acting on proactive inhibitory control via the α2-adrenoceptor. We suggest that targeting noradrenergic dysfunction may represent a new treatment approach in some of the movement initiation disorders seen in Parkinson’s disease.

Efficacy of 2-Hydroxyflavanone in Rodent Models of Pain and Inflammation: Involvement of Opioidergic and GABAergic Anti-Nociceptive Mechanisms.

The current work examined the pharmacological potential of a selected flavanone derivative 2-hydroxyflavanone as a promising remedy for the treatment and management of pain. The selected flavanone derivative (2-HF) was evaluated for its analgesic and anti-inflammatory potentials following standard pharmacological protocols including hot plate, acetic acid-induced writhing and tail immersion tests. Naloxone and pentylenetetrazol were used to evaluate the potential implication of GABAergic and opioidergic mechanisms. The anti-inflammatory potential of 2-HF was confirmed using carrageenan-, serotonin- and histamine-induced paw edema models as well as a xylene-induced ear edema model. Furthermore, the anti-neuropathic potential of 2-HF was tested using a cisplatin-induced neuropathic pain model. Our sample, at the tested concentrations of 15, 30 and 45 mg kg−1, showed considerable analgesic, anti-inflammatory effects, as well as efficacy against neuropathic pain. Naloxone and pentylenetetrazol at 1 and 15 mg kg−1 antagonized the anti-nociceptive activities of 2-hydroxyflavanone indicating the involvement of opioidergic and GABAergic mechanisms. In the static allodynia model, combination of gabapentin 75 mg kg−1 with 2-HF at 15, 30, 45 mg kg−1 doses exhibited considerable efficacy. In cold allodynia, 2-hydroxyflavanone, at doses of 15, 30 and 45 mg kg−1 and in combination with gabapentin (75 mg kg−1), demonstrated prominent anti-allodynic effects. The paw withdrawal latency was considerably increased in gabapentin + cisplatin treated groups. Moreover, cisplatin + 2-hydroxyflavanone 15, 30, 45 mg kg−1 showed increases in paw withdrawal latency. Likewise, considerable efficacy was observed for 2-hydroxyflavanone in thermal hyperalgesia and dynamic allodynia models. Our findings suggest that 2-hydroxyflavanone is a potential remedy for pain syndrome, possibly mediated through opioidergic and GABAergic mechanisms.

Regulation of heart rate following genetic deletion of the ß1 adrenergic receptor in larval zebrafish.

AimAlthough zebrafish are gaining popularity as biomedical models of cardiovascular disease, our understanding of their cardiac control mechanisms is fragmentary. Our goal was to clarify the controversial role of the ß1‐adrenergic receptor (AR) in the regulation of heart rate in zebrafish.MethodsCRISPR‐Cas9 was used to delete the adrb1 gene in zebrafish allowing us to generate a stable adrb1 −/− line. Larval heart rates were measured during pharmacological protocols and with exposure to hypercapnia. Expression of the five zebrafish adrb genes were measured in larval zebrafish hearts using qPCR.ResultsCompared with genetically matched wild‐types (adrb1 +/+ ), adrb1 −/− larvae exhibited ~20 beats min−1 lower heart rate, measured from 2 to 21 days post‐fertilization (dpf). Nevertheless, adrb1 −/− larvae exhibited preserved positive chronotropic responses to pharmacological treatment with AR agonists (adrenaline, noradrenaline, isoproterenol), which were blocked by propranolol (general ß‐AR antagonist). Regardless of genotype, larvae exhibited similar increases in heart rate in response to hypercapnia (1% CO2) at 5 dpf, but tachycardia was blunted in adrb1 −/− larvae at 6 dpf. adrb1 gene expression was abolished in the hearts of adrb1 −/− larvae, confirming successful knockout. While gene expression of adrb2a and adrb3a was unchanged, adrb2b and adrb3b mRNA levels increased in adrb1 −/− larval hearts.ConclusionDespite adrb1 contributing to the setting of resting heart rate in larvae, it is not strictly essential for zebrafish, as we generated a viable and breeding adrb1 −/− line. The chronotropic effects of adrenergic stimulation persist in adrb1 −/− zebrafish, likely due to the upregulation of other ß‐AR subtypes.

Morphine versus methadone for neonatal opioid withdrawal syndrome: a randomized controlled pilot study

BackgroundNeonatal Opioid Withdrawal Syndrome (NOWS) is a significant public health issue and while millions of neonates are affected each year, an optimal pharmacologic weaning protocol has yet to be demonstrated. In this study, we compare hospital length of stay (LOS) and length of treatment (LOT) for treatment of neonatal opioid withdrawal (NOWS) with morphine versus methadone.MethodsThis was a single-site, open-label, randomized controlled pilot study conducted from October 2016-September 2018. Infants were eligible if their primary in-utero drug exposure was heroin, oral opioids, or methadone and they were born at greater than or equal to 34 weeks gestation. Infants were excluded for serious medical comorbidities and primary in-utero exposure to buprenorphine.ResultsSixty-one infants were enrolled; 30 were randomized to methadone treatment, and 31 to morphine treatment. Overall 46% of infants required treatment for NOWS. LOS and LOT for infants treated with morphine was 17.9 days and 14.7 days respectively, compared to 16.1 days and 12.8 days for babies treated with methadone (p = 0.5, p = 0.54). Infants treated with morphine received lower total morphine equivalents than those treated with methadone (9.7 vs. 33, p < 0.01). Three treated infants in the methadone group required transfer to the Neonatal Intensive Care Unit, versus no infants in the morphine group.ConclusionsInfants treated with morphine versus methadone had no significant differences in LOS or LOT in this pilot study. Infants treated with methadone received up to 3 times the opioid based on morphine equivalents as infants treated with morphine and had more transfers to the NICU for over sedation.Clinical trial registrationMorphine Versus Methadone for Opiate Exposed Infants With Neonatal Abstinence Syndrome NCT02851303, initiated 01/08/2016.

LSD1 Inhibition Enhances the Immunogenicity of Mesenchymal Stromal Cells by Eliciting a dsRNA Stress Response.

Mesenchymal stromal cells (MSCs) are commonly known for their immune-suppressive abilities. However, our group provided evidence that it is possible to convert MSCs into potent antigen presenting cells (APCs) using either genetic engineering or pharmacological means. Given the capacity of UM171a to trigger APC-like function in MSCs, and the recent finding that this drug may modulate the epigenome by inhibiting the lysine-specific demethylase 1 (LSD1), we explored whether the direct pharmacological inhibition of LSD1 could instill APC-like functions in MSCs akin to UM171a. The treatment of MSCs with the LSD1 inhibitor tranylcypromine (TC) elicits a double-stranded (ds)RNA stress response along with its associated responsive elements, including pattern recognition receptors (PRRs), Type-I interferon (IFN), and IFN-stimulated genes (ISGs). The net outcome culminates in the enhanced expression of H2-Kb, and an increased stability of the cell surface peptide: MHCI complexes. As a result, TC-treated MSCs stimulate CD8 T-cell activation efficiently, and elicit potent anti-tumoral responses against the EG.7 T-cell lymphoma in the context of prophylactic vaccination. Altogether, our findings reveal a new pharmacological protocol whereby targeting LSD1 in MSCs elicits APC-like capabilities that could be easily exploited in the design of future MSC-based anti-cancer vaccines.

A Critical Review of the Antimicrobial and Antibiofilm Activities of Green-Synthesized Plant-Based Metallic Nanoparticles.

Metallic nanoparticles (MNPs) produced by green synthesis using plant extracts have attracted huge interest in the scientific community due to their excellent antibacterial, antifungal and antibiofilm activities. To evaluate these pharmacological properties, several methods or protocols have been successfully developed and implemented. Although these protocols were mostly inspired by the guidelines from national and international regulatory bodies, they suffer from a glaring absence of standardization of the experimental conditions. This situation leads to a lack of reproducibility and comparability of data from different study settings. To minimize these problems, guidelines for the antimicrobial and antibiofilm evaluation of MNPs should be developed by specialists in the field. Being aware of the immensity of the workload and the efforts required to achieve this, we set out to undertake a meticulous literature review of different experimental protocols and laboratory conditions used for the antimicrobial and antibiofilm evaluation of MNPs that could be used as a basis for future guidelines. This review also brings together all the discrepancies resulting from the different experimental designs and emphasizes their impact on the biological activities as well as their interpretation. Finally, the paper proposes a general overview that requires extensive experimental investigations to set the stage for the future development of effective antimicrobial MNPs using green synthesis.

Practical outpatient management of worsening chronic heart failure.

Management of worsening heart failure (WHF) has traditionally been hospital‐based, but with the rising burden of heart failure (HF), the pressure on healthcare systems exerted by this disease necessitates a different strategy than long (and costly) hospital stays. A strategy for outpatient intravenous (IV) diuretic treatment of WHF has been developed in certain American centres in the past 10 years, whereas European centres have been mostly favouring ‘classic’ in‐hospital management of WHF. Embracing novel, outpatient approaches for treating WHF could substantially reduce the burden on healthcare systems while improving patient's satisfaction and quality of life. The present article is intended to provide essential knowledge and practical guidelines aimed at helping clinicians implement these new ambulatory approaches using day hospital and/or at‐home hospitalization. The topics addressed by our group of HF experts include the pathophysiological background of diuretic therapy, the most suitable profile of WHF that may be managed in an ambulatory setting, the pharmacological protocols that can be used, as well as a detailed description of healthcare structures that can be proposed to deliver these ambulatory care interventions. The practical aspects of day hospital and hospital‐at‐home IV diuretic administration are specifically emphasized. The algorithm provided along with the practical IV diuretic protocols should assist HF clinicians in implementing this new approach in their local clinical setting.

Tocilizumab en pacientes COVID-19: evaluación del perfil de seguridad en una indicación off label

Tocilizumab (TCZ) is a new therapeutic alternative for severe cases of COVID-19 pneumonia. To evaluate the cumulative incidence (CI) of suspected adverse drug reactions (ADR) from TCZ in adult patients with COVID-19. An active pharmacological surveillance protocol was carried out in patients older than 18 years old, who received at least one dose of TCZ between May and August 2020 at a clinical hospital. Non-infectious ADRs were categorized according to the Common Terminology Criteria for Adverse Events and the development of infection was classified as present or absent. Causality and preventability of ADRs were determined with the Naranjo Algorithm and the modified Schumock & Thornton criteria, respectively. The CI of ADRs caused by TCZ was 69.6% (95% confidence intervals (CI): 63.5-76.6). A rise in alanine and aspartate aminotransferases and the development of infections were the most frequent adverse events. Seventy-four percent were considered mild in severity. Sixty two percent of suspected non-infectious ADRs were classified as probable and all the infectious events as Possible. Of the ADRs observed, 33% were preventable. The occurrence of ADRs after the use of TCZ is frequent, of mild severity, and in one third of the cases, preventable. We suggest monitoring blood count, liver function tests and ruling out infection prior to TCZ administration.

Treatments and therapeutic protocols for the recovery of anasphyxiated new-born: Areview ofpre-clinical and clinical studies inhuman neonates and indifferent animal models.

The objective ofthis review is toascertain the advantages and disadvantages ofseveral treatments and therapeutic protocols that have been used for the prevention and treatment ofperinatal asphyxia inhuman neonates and indifferent animal models. Perinatal asphyxia isone ofthe main causes ofmortality worldwide and isanimportant factor intriggering physio-metabolic disorders that result inserious neurological consequences and learning disorders not only inhuman foetuses and neonates, but also inanimals. Inrecent years, the search for new pharmacological protocols toprevent and reverse physio-metabolic disorders and brain damage derived from perinatal asphyxia has been and continues to bethe subject ofintense research. Currently, within these pharmacological protocols, therapeutic strategies have been evaluated that use respiratory and hormonal stimulants, aswell ashypothermic therapies incombination with other putative neuroprotective agents. Similarly, energy supplements have been evaluated with the objective ofpreventing perinatal asphyxia and treating new-borns with this condition, and todecrease the incidence ofneonatal and foetal deaths associated with it. However, despite these promising advances, this pathology has persisted, since the administration ofthese therapies inlow doses may not exert aneuroprotective effect or, inhigh doses, can trigger adverse effects (such asreduced cardiac contractility, reduced cerebral blood flow, poor perfusion, sympathetic and neuroendocrine stimulation, and increased blood viscosity) inhuman foetuses and neonates aswell as indifferent animal models (rats, piglets, sheep and rabbits). Therefore, it isimportant todetermine the minimum effective dose with which these therapies exert aneuroprotective effect, aswell asthemode ofadministration, theduration oftherapy, etc. Therefore, until apowerful strategy isfound toimprove the consequences ofsuffocation, this topic will continue to bethe subject ofintensive research inthe future.

Inadequate hypertension control rates: A global concern for countries of all income levels.

Inadequate hypertension control rates: A global concern for countries of all income levels.

Engineered fluidic device to achieve multiplexed monitoring of cell cultures with digital holographic microscopy.

We present a low-cost, 3D-printed, and biocompatible fluidic device, engineered to produce laminar and homogeneous flow over a large field-of-view. Such a fluidic device allows us to perform multiplexed temporal monitoring of cell cultures compatible with the use of various pharmacological protocols. Therefore, specific properties of each of the observed cell cultures can be discriminated simultaneously during the same experiment. This was illustrated by monitoring the agonists-mediated cellular responses, with digital holographic microscopy, of four different cell culture models of cystic fibrosis. Quantitatively speaking, this multiplexed approach provides a time saving factor of around four to reveal specific cellular features.

Pharmacologically Induced Ex Copula Ejaculation in Horses and Donkeys.

Pharmacologically induced ex copula ejaculation is a method used for collection of semen when the traditional methods of semen collection are not feasible. Common indications for this method include health issues that either preclude the physical act of mating or result in impaired erection and ejaculation. The method also offers an alternative when there is a lack of equipment and facilities required for semen collection using the conventional artificial vagina method. A variety of pharmacological protocols for ex copula ejaculation in stallions have been evaluated in both research and clinical settings with no serious side-effects reported. In general, these protocols included tricyclic antidepressants, alpha-2 adrenergic receptor agonists, and smooth muscle stimulators, either individually or in combination. Although there is a lot of variation in the ejaculatory rates among studies, a combination of imipramine and xylazine appears to be an effective option for inducing ejaculation in stallions. In cases where this protocol is not successful, collections should be reattempted using a combination of imipramine, detomidine, and oxytocin. Regardless of the protocol used, a quiet environment with minimal disturbance is associated with a better outcome. In contrast to the body of literature available on pharmacologically induced ex copula ejaculation in horses, only a few studies have been published so far on this topic in donkeys. Further studies are warranted to investigate whether pharmacologically induced ex copula ejaculation is an effective method of semen collection in jacks and to compare different pharmacological protocols for inducing ejaculation in jacks.

Chronic vs non-chronic depression in psychiatric inpatient care - Data from a large naturalistic multicenter trial

BackgroundAround 20% - 30% of depressed individuals experience a chronic form of depression lasting two or more years. This naturalistic study investigates the characteristics and the course of chronic depressed patients (CD) during standard antidepressant treatment in comparison to not chronically depressed (NCD) patients. MethodsData of 954 patients were drawn from the prospective naturalistic, multicenter study of the German research network on depression, CD was met as classifier by 113 patients (11.8%), whereas 841 patients (88.2%) had non-chronic courses (NCD). ResultsCD was significantly associated with a low age at onset, use of benzodiazepines, psychotherapy at baseline, substance abuse, a depressive personality disorder and a low degree of extraversion. CD patients showed a longer hospital stay, lower remission rates, increased rates of suicidal ideation as well as higher depression scores at discharge. In addition, individuals with chronic depression continued to obtain higher neuroticism scores and lower extraversion scores at discharge. LimitationResults were assessed by a post-hoc analysis, based on prospectively collected data. ConclusionCD patients have an inferior outcome in clinical measures as well as personality dimensions (i.e. low extraversion) compared to non-CD patients. These findings support the notion that CD patients entering a setting of standard psychiatric inpatient care will show less benefit compared to non-CD patients, and that this difference as such may be used as a stratifying marker for providing specialized psychiatric treatment with optimized pharmacological and psychotherapeutic protocols.