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Archives of Razi Institute Dec 2023Foot-and-mouth disease (FMD) has a high prevalence in cloven-hoofed animals. It is also highly contagious and remains a serious threat to livestock worldwide. Despite... (Comparative Study)
Comparative Study
Foot-and-mouth disease (FMD) has a high prevalence in cloven-hoofed animals. It is also highly contagious and remains a serious threat to livestock worldwide. Despite the widespread vaccination program in Iran, outbreaks of FMD continue to occur. Vaccination is one of the most effective methods of preventing FMD. The vaccines used in Iran are of the inactivated type and contain several serotypes. Since inactivated vaccines without adjuvants do not induce a high and durable antibody response, it is necessary to use adjuvants. Montanide ISA 206 VG is a mineral oil-based adjuvant that produces a water-in-oil-in-water (w:o:w) emulsion in vaccine preparations. However, a large number of manufacturers in Iran and around the world still use alum adjuvant (with or without saponin) to produce the FMD vaccine. This study used Montanide ISA 206 and alum adjuvants to administer the O2010 serotype of the FMD virus to goats. A total of six goats were divided randomly into three groups. Vaccines were administered subcutaneously twice, at a one-month interval. Blood sampling was done at different times, and the micro-neutralization method was used to measure the neutralizing antibody titer in each serum. Seven days after the second vaccination, the alum group's antibody titer was higher but not statistically significant. However, from the 28th day after the second injection until the end of the study, the Montanide ISA 206 group's antibody titer was significantly higher than that of the alum group. Six months after the second injection, the antibody titer in the ISA 206 group remained at the peak level, while in the alum group, it decreased and reached the minimum protective level. Nine months after the second injection, the antibody titer remained at its peak level in the ISA 206 group, whereas it dropped significantly in the alum group. Based on the findings, ISA 206 VG is capable of generating long-term humoral immunity in goats against the FMD serotype O2010 and could replace aluminum hydroxide adjuvants in FMD vaccine preparations.
Topics: Animals; Goats; Aluminum Hydroxide; Foot-and-Mouth Disease Virus; Goat Diseases; Foot-and-Mouth Disease; Adjuvants, Immunologic; Viral Vaccines; Antibodies, Neutralizing; Antibodies, Viral; Iran; Oleic Acids; Mannitol
PubMed: 38828163
DOI: 10.32592/ARI.2023.78.6.1843 -
Drug Design, Development and Therapy 2024Henagliflozin is an original, selective sodium-glucose cotransporter 2 (SGLT2) inhibitor. Hydrochlorothiazide (HCTZ) is a common anti-hypertensive drug. This study aimed...
PURPOSE
Henagliflozin is an original, selective sodium-glucose cotransporter 2 (SGLT2) inhibitor. Hydrochlorothiazide (HCTZ) is a common anti-hypertensive drug. This study aimed to evaluate the potential interaction between henagliflozin and HCTZ.
METHODS
This was a single-arm, open-label, multi-dose, three-period study that was conducted in healthy Chinese volunteers. Twelve subjects were treated in three periods, period 1: 25 mg HCTZ for four days, period 2: 10 mg henagliflozin for four days and period 3: 25 mg HCTZ + 10 mg henagliflozin for four days. Blood samples and urine samples were collected before and up to 24 hours after drug administrations on day 4, day 10 and day 14. The plasma concentrations of henagliflozin and HCTZ were analyzed using LC-MS/MS. The urine samples were collected for pharmacodynamic glucose and electrolyte analyses. Tolerability was also evaluated.
RESULTS
The 90% CI of the ratio of geometric means (combination: monotherapy) for AUC of henagliflozin and HCTZ was within the bioequivalence interval of 0.80-1.25. For henagliflozin, co-administration increased C by 24.32% and the 90% CI of the GMR was (108.34%, 142.65%), and the 24-hour urine volume and glucose excretion decreased by 0.43% and 19.6%, respectively. For HCTZ, co-administration decreased C by 19.41% and the 90% CI of the GMR was (71.60%, 90.72%), and the 24-hour urine volume and urinary calcium, potassium, phosphorus, chloride, and sodium excretion decreased by 11.7%, 20.8%, 11.8%, 11.9%, 22.0% and 15.5%, respectively. All subjects (12/12) reported adverse events (AEs), but the majority of theses AEs were mild and no serious AEs were reported.
CONCLUSION
Although C was affected by the combination of henagliflozin and HCTZ, there was no clinically meaningful safety interaction between them. Given these results, coadministration of HCTZ should not require any adaptation of henagliflozin dosing.
TRIAL REGISTRATION
ClinicalTrials.gov NCT06083116.
Topics: Humans; Hydrochlorothiazide; Healthy Volunteers; Adult; Male; Drug Interactions; Young Adult; Female; Glucosides; Asian People; Dose-Response Relationship, Drug; Sodium-Glucose Transporter 2 Inhibitors; East Asian People
PubMed: 38828023
DOI: 10.2147/DDDT.S433377 -
Clinical Case Reports Jun 2024Peripartum cardiomyopathy (PPCM) is a rare cause of heart failure associated with pregnancy without any other known cause. With a prognosis that can vary from the...
KEY CLINICAL MESSAGE
Peripartum cardiomyopathy (PPCM) is a rare cause of heart failure associated with pregnancy without any other known cause. With a prognosis that can vary from the complete recovery of left ventricular function to maternal mortality as well as recurrence with subsequent pregnancies, early diagnosis and treatment of PPCM is important in management. Bromocriptine treatment is beneficial effects on LVEF and mortality in women with severe acute PPCM in addition to standard heart failure therapy. However, further study is required to establish its effect in PPCM.
ABSTRACT
Peripartum cardiomyopathy (PPCM) is a rare cause of heart failure associated with pregnancy without any other known cause. Most of the clinical presentation is similar to symptoms of advanced pregnancy making the diagnosis difficult. Reported are three patients who developed dyspnea, orthopnea, and dry cough during the first week of puerperium. On examination, bilateral lower limb edema and bilateral basal lung crepitation were present in all patients. Chest radiograph showed pulmonary edema in cases two and three, and pleural effusion in case one. All patients had reduced left ventricular ejection fraction and raised N-terminal pro-b-type natriuretic peptide (NT-proBNP) levels. Case two developed PPCM in the background of left pyelonephritis. Case three was complicated by acute kidney injury. All patients were managed with bromocriptine, diuretics, beta-blockers, ACE inhibitors, and fluid restriction. Hence, PPCM though rare should be considered as a differential in women presenting with features of heart failure in later months of pregnancy or within 5 months of delivery.
PubMed: 38827942
DOI: 10.1002/ccr3.9043 -
Journal of Cardiology Cases Jun 2024A 68-year-old man was diagnosed with pericarditis associated with immunoglobulin G4-related disease and was administered prednisolone 2 years prior to presentation....
UNLABELLED
A 68-year-old man was diagnosed with pericarditis associated with immunoglobulin G4-related disease and was administered prednisolone 2 years prior to presentation. During the process of tapering off from prednisolone 1 year later, edema of the lower legs and pleural effusion worsened. He gradually developed dyspnea on exertion, and laboratory examinations revealed elevated liver enzyme levels. Diuretics were administered; however, the symptoms did not resolve. Transthoracic echocardiography and cardiac catheterization revealed findings consistent with those of constrictive pericarditis. Pericardiectomy was considered and the perioperative risks due to possible recovery from liver dysfunction were discussed. Combinational elastography was subsequently performed. The results indicated the absence of liver fibrosis, suggesting that liver dysfunction was attributable to liver congestion; thus, the liver dysfunction was considered reversible. Subsequently, pericardiectomy was performed. Given that constrictive pericarditis can lead to liver dysfunction due to congestion, the perioperative risk is often controversial when considering surgical interventions.
LEARNING OBJECTIVE
Combinational elastography may be useful in the preoperative evaluation of patients with cardiac diseases complicated by liver dysfunction to distinguish liver fibrosis, understand the pathogenesis of liver dysfunction, and determine subsequent treatment strategies.
PubMed: 38826762
DOI: 10.1016/j.jccase.2024.02.006 -
Identification and expression profiling of microRNAs in leaf tissues of Mill. under salinity stress.Plant Signaling & Behavior Dec 2024Mill. commonly known as fennel, is a globally recognized aromatic medicinal plant and culinary herb with widespread popularity due to its antimicrobial, antioxidant,...
Mill. commonly known as fennel, is a globally recognized aromatic medicinal plant and culinary herb with widespread popularity due to its antimicrobial, antioxidant, carminative, and diuretic properties, among others. Although the phenotypic effects of salinity stress have been previously explored in fennel, the molecular mechanisms underlying responses to elevated salinity in this plant remain elusive. MicroRNAs (miRNAs) are tiny, endogenous, and extensively conserved non-coding RNAs (ncRNAs) typically ranging from 20 to 24 nucleotides (nt) in length that play a major role in a myriad of biological functions. In fact, a number of miRNAs have been extensively associated with responses to abiotic stress in plants. Consequently, employing computational methodologies and rigorous filtering criteria, 40 putative miRNAs belonging to 25 different families were characterized from fennel in this study. Subsequently, employing the psRNATarget tool, a total of 67 different candidate target transcripts for the characterized fennel miRNAs were predicted. Additionally, the expression patterns of six selected fennel miRNAs (i.e. fvu-miR156a, fvu-miR162a-3p, fvu-miR166a-3p, fvu-miR167a-5p, fvu-miR171a-3p, and fvu-miR408-3p) were analyzed under salinity stress conditions via qPCR. This article holds notable significance as it identifies not only 40 putative miRNAs in fennel, a non-model plant, but also pioneers the analysis of their expression under salinity stress conditions.
Topics: Foeniculum; MicroRNAs; Plant Leaves; Salt Stress; Gene Expression Regulation, Plant; Gene Expression Profiling; RNA, Plant
PubMed: 38825852
DOI: 10.1080/15592324.2024.2361174 -
BMC Emergency Medicine Jun 2024This study assesses the influence of hyperkalemia on both disease severity and the risk of mortality among patients admitted to the emergency room. (Observational Study)
Observational Study
OBJECTIVE
This study assesses the influence of hyperkalemia on both disease severity and the risk of mortality among patients admitted to the emergency room.
METHODS
This retrospective observational study utilized data from the Chinese Emergency Triage Assessment and Treatment database (CETAT, version 2.0), which was designed to evaluate and optimize management strategies for emergency room (ER) patients. Patients were systematically categorized based on serum potassium levels. Relationships between serum potassium levels, risk of mortality, and the severity of illness were then analyzed using multifactorial logistic regression and through Receiver Operating Characteristic (ROC) analysis. The effectiveness of various treatments at lowering potassium levels was also investigated.
RESULTS
12,799 emergency patients were enrolled, of whom 20.1% (n = 2,577) were hypokalemic and 2.98% (n = 381) were hyperkalemic. Among hyperkalemic patients, the leading reasons for visiting the ER were altered consciousness 23.88% (n = 91), cardiovascular symptoms 22.31% (n = 85), and gastrointestinal symptoms 20.47% (n = 78). Comparative analysis with patients exhibiting normal potassium levels revealed hyperkalemia as an independent factor associated with mortality in the ER. Mortality risk appears to positively correlate with increasing potassium levels, reaching peaks when blood potassium levels ranged between 6.5 and 7.0. Hyperkalemia emerged as a strong predictor of death in the ER, with an Area Under the Curve (AUC) of 0.89. The most frequently prescribed treatment for hyperkalemia patients was diuretics (57.32%, n = 188), followed by intravenous sodium bicarbonate (50.91%, n = 167), IV calcium (37.2%, n = 122), insulin combined with high glucose (27.74%, n = 91), and Continuous Renal Replacement Therapy (CRRT) for 19.82% (n = 65). Among these, CRRT appeared to be the most efficacious at reducing potassium levels. Diuretics appeared relatively ineffective, while high-glucose insulin, sodium bicarbonate, and calcium preparations having no significant effect on the rate of potassium decline.
CONCLUSION
Hyperkalemia is common in emergency situations, especially among patients with altered consciousness. There is a strong positive correlation between the severity of hyperkalemia and mortality risk. CRRT appears to be the most effective potassium reducting strategy, while the use of diuretics should be approached with caution.
Topics: Adult; Aged; Female; Humans; Male; Middle Aged; China; Emergency Service, Hospital; Hospital Mortality; Hyperkalemia; Intensive Care Units; Potassium; Retrospective Studies; ROC Curve; Severity of Illness Index; Patient Admission
PubMed: 38824546
DOI: 10.1186/s12873-024-01011-z -
Clinical Hypertension Jun 2024Obstructive sleep apnea (OSA) is associated with high blood pressure that responds poorly to usual antihypertensive therapy.
BACKGROUND
Obstructive sleep apnea (OSA) is associated with high blood pressure that responds poorly to usual antihypertensive therapy.
METHODS AND RESULTS
Forty-one subjects with OSA had 25% higher plasma norepinephrine and 42% higher epinephrine measured every 2 h over 24 h than 20 control subjects. They also excreted more sodium during sleep. This suggested that that a sympatholytic would be a more successful antihypertensive than a diuretic. To test this hypothesis we treated a second group of 23 hypertensive apneics with placebo, 6 weeks of the sympatholytic guanfacine and 6 weeks of hydrochlorothiazide in a crossover study. Guanfacine lowered 24-hour blood pressure by 9.6/6.7 mmHg, more than the 5.4/2.9 mmHg effect of hydrochlorothiazide (P < 0.05). Nighttime systolic blood pressure dipping was poor at 6.6 ± 1.8%. Hydrochlorothiazide did not alter blood pressure dipping but guanfacine improved dipping to 9.1 ± 1.2%, a better result (P = 0.03) than from the diuretic. Central aortic pressure by pulse wave analysis was 120/84 mmHg on hydrochlorothiazide and 109/72 on guanfacine, (P < 0.05). Guanfacine, but not hydrochlorothiazide, improved baroreflex sensitivity, heart rate variability and flow mediated vascular dilation, suggesting that decreasing the elevated sympathetic nerve activity of obstructive sleep apnea returned vascular function toward normal.
CONCLUSIONS
OSA is the most common condition associated with antihypertensive treatment failure. It increased sympathetic nerve activity day and night. Drugs that block sympathetic nerve function are not among the 4 most commonly recommended classes of antihypertensives but diuretics are. Sympatholytic therapy was superior to diuretic treatment for hypertension associated with sleep apnea.
TRIAL REGISTRATION
NCT, NCT02699125, Registered 26 February 2016 - Retrospectively registered, https://clinicaltrials.gov/study/NCT02699125 .
PubMed: 38822391
DOI: 10.1186/s40885-024-00272-x -
BJS Open May 2024Readmission rates following ileostomy formation are high. Dehydration and consecutive renal failure are common causes of readmission, potentially pronounced by drugs...
Preoperative use of angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers and diuretics increases the risk of dehydration after ileostomy formation: population-based cohort study.
BACKGROUND
Readmission rates following ileostomy formation are high. Dehydration and consecutive renal failure are common causes of readmission, potentially pronounced by drugs affecting the homeostasis. The aim of the study was to assess the risk of dehydration after ileostomy formation in patients treated with angiotensin-converting enzyme inhibitors (ACEI), angiotensin II receptor blockers (ARB) or diuretics.
METHOD
This nationwide population-based cohort study used data derived from the Colorectal Cancer Data Base of several Swedish healthcare registers. The study included all patients operated on with elective anterior resection and temporary ileostomy for rectal cancer clinically staged I-III in Sweden in 2007-2016. Exposure was at least two dispensations of ACEI, ARB or diuretics within 1 year prior to surgery. Outcome was 90-day readmission due to dehydration including acute renal failure.
RESULTS
In total, 3252 patients were included with 1173 (36.1%) exposed to ACEI, ARB or diuretics. The cumulative incidence for 90-day readmission due to dehydration was 29.0% (151 of 520) for exposed versus 13.8% (98 of 712) for unexposed. The proportion of readmissions due to any reason was 44.3% (520 of 1173) for exposed compared to 34.2% (712 of 2079) for unexposed. The incidence rate ratio for readmission due to dehydration was 2.83 (95% c.i. 2.21 to 3.63, P < 0.001). The hazard rate ratio was 2.45 (95% c.i. 1.83 to 3.27, P < 0.001) after adjusting for age, gender and comorbidity.
CONCLUSION
Medication with ACEI, ARB or diuretics defines a vulnerable patient group with increased risk of readmission due to dehydration after ileostomy formation.
Topics: Humans; Male; Female; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Aged; Ileostomy; Sweden; Dehydration; Middle Aged; Patient Readmission; Diuretics; Risk Factors; Rectal Neoplasms; Postoperative Complications; Cohort Studies; Aged, 80 and over; Incidence; Registries; Preoperative Care
PubMed: 38818959
DOI: 10.1093/bjsopen/zrae051 -
Frontiers in Endocrinology 2024Polycystic ovary syndrome (PCOS) is often associated with metabolic-associated fatty liver disease (MAFLD). MAFLD has been associated with altered hepatic function,... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Polycystic ovary syndrome (PCOS) is often associated with metabolic-associated fatty liver disease (MAFLD). MAFLD has been associated with altered hepatic function, systemic dysmetabolism, and abnormal circulating levels of signaling molecules called organokines. Here, we assessed the effects of two randomized treatments on a set of organokines in adolescent girls with PCOS and without obesity, and report the associations with circulating biomarkers of liver damage, which were assessed longitudinally in the aforementioned studies as safety markers.
MATERIALS AND METHODS
Liver enzymes [aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyl transferase (GGT)] were assessed as safety markers in previous randomized pilot studies comparing the effects of an oral contraceptive (OC) with those of a low-dose combination of spironolactone-pioglitazone-metformin (spiomet) for 1 year. As a endpoint, the organokines fibroblast growth factor-21 (FGF21), diazepam-binding protein-1 (DBI), and meteorin-like protein (METRNL) were assessed by ELISA after 6 months of OC (N = 26) or spiomet (N = 28). Auxological, endocrine-metabolic, body composition (using DXA), and abdominal fat partitioning (using MRI) were also evaluated. Healthy, age-matched adolescent girls (N = 17) served as controls.
RESULTS
Circulating ALT and GGT levels increased during OC treatment and returned to baseline concentrations in the post-treatment phase; in contrast, spiomet treatment elicited no detectable changes in ALT and GGT concentrations. In relation to organokines after 6 months of treatment, (1) FGF21 levels were significantly higher in PCOS adolescents than in control girls; (2) DBI levels were lower in OC-treated girls than in controls and spiomet-treated girls; and (3) no differences were observed in METRNL concentrations between PCOS girls and controls. Serum ALT and GGT levels were directly correlated with circulating METRNL levels only in OC-treated girls (R = 0.449, P = 0.036 and R = 0.552, P = 0.004, respectively).
CONCLUSION
The on-treatment increase in ALT and GGT levels occurring only in OC-treated girls is associated with circulating METRNL levels, suggesting enhanced METRNL synthesis as a reaction to the hepatic changes elicited by OC treatment.
CLINICAL TRIAL REGISTRATION
https://doi.org, identifiers 10.1186/ISRCTN29234515, 10.1186/ISRCTN11062950.
Topics: Humans; Female; Polycystic Ovary Syndrome; Adolescent; Metformin; Fibroblast Growth Factors; Liver; Alanine Transaminase; Pioglitazone; Biomarkers; Spironolactone; Aspartate Aminotransferases; gamma-Glutamyltransferase; Non-alcoholic Fatty Liver Disease; Contraceptives, Oral; Hypoglycemic Agents
PubMed: 38818508
DOI: 10.3389/fendo.2024.1325230 -
Acta Pharmaceutica (Zagreb, Croatia) Jun 2024At present, society has embraced the fact apropos population aging and climate changes, that demand, amongst others, innovative pharmaceutical technologies, emphasising...
At present, society has embraced the fact apropos population aging and climate changes, that demand, amongst others, innovative pharmaceutical technologies, emphasising the development of patient-specific delivery systems and thus the provision of efficient and sustainable drugs. Protein drugs for subcutaneous administration, by allowing less frequent application, represent one of the most important parts of the pharmaceutical field, but their development is inevitably faced with obstacles in providing protein stability and suitable formulation viscosity. To gain further knowledge and fill the gaps in the already constructed data platform for the development of monoclonal antibody formulations, we designed a study that examines small model proteins, bovine serum albumin. The main aim of the presented work is to evaluate the effect of protein concentrations on critical quality attributes of both, pre-lyophilised liquid formulations, and lyophilised products. Through the study, the hypothesis that increasing protein concentration leads to higher viscosity and higher reconstitution time without affecting the stability of the protein was confirmed. The most important finding is that sucrose plays a key role in the lyophilisation of investigated protein, nevertheless, it can be predicted that, to ensure the beneficial effect of mannitol, its amount has to prevail over the amount of sucrose.
Topics: Freeze Drying; Serum Albumin, Bovine; Viscosity; Drug Compounding; Humans; Sucrose; Drug Stability; Chemistry, Pharmaceutical; Excipients; Mannitol; Protein Stability
PubMed: 38815206
DOI: 10.2478/acph-2024-0013