Low-dose versus standard-dose alteplase for intravenous thrombolysis in patients with acute ischemic stroke in Iran: Results from the safe implementation of treatments in stroke registry

Background: Rates of intracranial hemorrhage (ICH) after intravenous thrombolysis (IVT) differ depending regard are scarce in the Middle Eastern region. Methods: The present retrospective study was performed on data extracted from the Safe Implementation of Treatments in Stroke (SITS) registry. Computed tomography (CT) image analysis was based on the SITS-Monitoring Study (SITS-MOST) definition for symptomatic ICH (SICH). Functional outcome at 3 months was assessed using the modified Rankin Scale (mRS). Multivariate logistic regression including adjusted analysis was used for comparison between groups. Results: Of 6615 patients, 1055 were enrolled. A total of 86% (n = 906) received a standard dose and 14% (n = 149) received a low dose of alteplase. Favorable 3-month outcome was achieved in 481 (53%) patients in the standard group and 71 (48%) patients in the low-dose group [adjusted odds ratio (AOR) = 1.24, 95% confidence interval (CI): 0.87-1.75, P = 0.218]. SICH occurred in 14 (1.5%) patients in the standard group and 3 (2%) patients in the low-dose group [odds ratio (OR) = 2.77, 95% CI: 0.36-21.04, P = 0.120]. At 3 months, mortality occurred in 145 (16.0%) patients in the standard group and 29 (19.4%) patients in the low-dose group (OR = 1.22, 95% CI: 0.78-1.91, P = 0.346). Conclusion: Low-dose compared to standard-dose alteplase for patients with acute ischemic stroke (AIS) was not associated with fewer hemorrhagic events and there was no significant difference in the favorable 3-month outcome (mRS: 0-2) or mortality rate.

PATHOLOGY OF EQUINE INFECTION WITH SALMONELLA TYPHIMPRIUM VAR COPENHAGEN

Twelve horses were divided into three equal groups. Group I animals were inoculated orally with (3.7 X1012)CFU of a highly virulent strain of Salmonella typhimurium 3,;a_r cop§_n__hagen. Group 11 animals were inoculated orally with 2 doses of Salmonella and then challenged with a high dose. Group III horses, served as non - infected control. ‘ The main lesions were primarily confined to the digestive tract and were characterized by catarrhal enteritis. Pseudornembrane covered the mucosa of the ileum at the ileo — cecal Valve region. Histopathological examination revealed marked rnononuclear cellular infiltration in the lamina propria and occasionally necrosis and edema in the mucosa and submucosa of the intestine.

Effect of Natural Chinese Herbal Supplements (TCMF4) on Lactation Performance and Serum Biomarkers in Peripartal Dairy Cows

This study examined the effect of mixed medicinal herbs from China in the ground form on milk yield and various blood metabolites before and after parturition in Holstein cows. Crushed Agastache rugosus, Scutellaria barbata, Pericarpium citri reticulate, and Radix glycyrrhizae were used to develop TCMF4. Thirty-two Chinese Holstein cows were randomly divided into a control group or groups receiving 0.1, 0.3, or 0.5 kg TCMF4/cow/d from −7 through 21 d relative to parturition. Blood samples for serum isolation were collected at −7, −1, 1, 7, 14, and 21 d relative to parturition and used to measure glucose, β-hydroxybutyric acid (BHBA), total protein, albumin, globulin, and alkaline phosphatase. Milk production was recorded daily for the first 21 d postpartum, and composition was analyzed at 7, 14, and 21 d. Data were analyzed using a one-way analysis of variance (ANOVA) for multiple comparisons. The average milk production during the first 21-d postpartum was 28.7 ± 6.9, 27.2 ± 7.1, 31.2 ± 6.8, and 38.5 ± 6.1 kg/d for control group and groups receiving 0.1, 0.3, or 0.5 kg TCMF4. Thus, average daily milk production increased between 9 to 34% by supplementation with TCMF4 compared with the control group. Compared with the control group, in the middle dose group, milk concentrations of lactose and total protein decreased by 21 and 19%, respectively, at d 7 around parturition, while total solids increased by 23% at d 21 in the high-dose group. Furthermore, compared with the control group, serum BHBA decreased by 50 and 20% at d −1 and 21 around parturition in the high-dose group. Overall, TCMF4 supplementation improved dry matter intake (DMI) and milk production of dairy cows during the periparturient period without adverse effects on liver function, and plasma BHBA concentrations of dairy cows tended to decrease when dietary TCMF4 increased, which suggested that TCMF4 might be used as potential additives in dairy cows to improve production performance.

Evaluation of Transplacental Antibody Transfer in SARS-CoV-2-Immunized Pregnant Women

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy could result in adverse perinatal outcome. Clinical data on the assessment of the immune response in vaccinated pregnant women and subsequent transplacental antibody transfer are quite limited. Objective: To assess maternal and neonatal neutralizing antibody levels against both wildtype and Delta (B.1.617.2) variants after maternal mRNA vaccination. Study Design: This cohort study was conducted 29 pregnant women who were vaccinated at least one dose of Moderna (mRNA-1273) vaccine. Both neutralizing antibody (wildtype and Delta variant) and S1 receptor binding domain IgG antibody levels were evaluated in maternal and cord blood on the day of delivery. Results: Superiority of antibody level was significant in fully vaccinated women compared with the one-dose group (maternal sera, median, 97.46%; cord sera, median, 97.37% versus maternal sera, median, 4.01%; cord sera, median, 1.44%). No difference in antibody level was noted in relation to interval of second immunization to delivery in the two-dose group (95.99% in 0–2 weeks, 97.45% in 2–4 weeks, 97.48% in 4–8 weeks, 97.72% in 8–10 weeks). The most pronounced reduction was observed for the Delta variant. The wildtype neutralizing antibody level of full-vaccinated women was not influenced by the pertussis vaccination. Conclusion: The data underscore the importance of full vaccination in pregnancy and support the recommendation of COVID-19 immunization for pregnant women. The lower level of vaccine-induced neutralizing antibodies for the Delta variant indicates insufficient protection for mother and newborn and highlights the need for development of effective vaccine strategies.

A phase I dose-escalation, safety/tolerability, and preliminary efficacy study of the intratumoral administration of GEN0101 in patients with advanced melanoma

Despite recent advance in immunotherapy agents, safe new therapies that enhance the effects of immune checkpoint inhibitors are still required to develop. We previously demonstrated that hemagglutinating virus of Japan-envelope (HVJ-E) induced not only direct tumor cell death but also antitumor immunity through the activation of T and natural killer (NK) cells, thereafter, developed a manufacturing process of HVJ-E (GEN0101) for clinical use. We here performed a phase Ia clinical trial of intratumoral GEN0101 administration in six patients with stage IIIC or IV malignant melanoma. The primary aim was to evaluate the safety and tolerability of GEN0101, and the secondary aim was to examine the objective tumor response. Patients were separated into two groups (n = 3 each) and received a low dose of 30,000 and high dose of 60,000 mNAU of GEN0101. All patients completed a two-week follow-up evaluation without severe adverse events. The overall response rate was 33% (2 of 6), with 2 partial responses in the high-dose group and 2 with stable disease, and 2 with progressive disease in the low-dose group. Local complete or partial responses were observed in 11 of 18 (61%) target lesions. One patient demonstrated shrinkage of lung metastases after the treatment. The activity of NK cells and interferon-γ levels were increased in the circulation, indicating augmentation of antitumor immunity by GEN0101. This trial showed not only the safety and tolerability but also the significant antitumor effect of GEN0101, suggesting that GEN0101 might be a promising new drug for patients with advanced melanoma.

Effect of Oxytocin on the Body Weight of Male Rabbits

This study was carried out to investigate the effect of two different doses of oxytocin on weight. Adult male rabbits (15) were weighed and provided with food twice daily for 3 weeks to determine the amount of food consumed daily and the time spent feeding by each rabbit. After 3 weeks the rabbits were weighed and divided randomly into 3groups: the control group, the low dose group, and the high dose group. The animals were injected daily for 3 weeks. During that time the amount of food consumed and the time spent feeding in both periods were determined. After the end of the treatment period the rabbits were weighed, and sacrificed. The results of this study showed that before treatment the rabbits consumed more food in the evening period than they did in the afternoon period. The mean time spent feeding in the evening period was slightly higher than that spent in the afternoon period; however, this difference was not statistically significant. After treatment, there was still significant difference between the means of the consumed food in the afternoon and the evening period for the control group. The mean amounts of food consumed in both periods by the treated groups were slightly reduced, but this reduction was not statistically significant. Furthermore, the mean time spent feeding in the evening period was slightly higher than that of the afternoon period for the 3 groups; however, these differences were not significant. The mean weight of the control group was slightly increased after treatment with the hormone; and the mean weights of the treated groups were slightly reduced after treatment. However, changes in body weighs were not statistically significant.

Effect of salicylidene salicylhydrazide on testes of albino mice: A histomorphological study.

Objectives: To evaluate salicylidene salicylhydrazide (SCS) for any possible toxicological effects on male reproductive system in Albino male BALB/c mice. Study Design: Experimental study. Study Setting: Department of Histopathology, Khyber Medical College Peshawar and Department of Pharmacy, University of Peshawar, Peshawar were utilized for conducting this study. Period: July, 2020 to December, 2020. Material & Methods: Male BALB/c mice were daily administered with SCS at 5, 25, and 50 mg/kg for 7 and 14 days. The body and testes weights were measured and the testes were subjected to histological tissue processing techniques. Results: The extent of testicular toxicity was evaluated by using modified Johnsen scoring system for assessing the level of spermatogenesis, and morphometric analysis by measuring the diameter of the seminiferous tubules, thickness of germinal epithelium, and area of interstitial cells of Leydig. The body and testes weights showed that the various doses of SCS have no substantial effects after 7 and 14 days. The tested doses of SCS did not produce any distinguishable change in the normal histological features of seminiferous tubules and interstitium after 7 days. However, after 14 days, the 50 mg/kg dose of SCS was associated with vacuolization and loosening of germinal epithelium. These mild-to-moderate histopathological aberrations was confirmed from morphometric analysis in this dose group in which a decrease in the seminiferous tubules’ diameter and reduction in the thickness of germinal epithelium along with an increase in the interstitial area were observed. Conclusion: These findings concluded that SCS is considered to be relatively safe.

Безопасностьометрия при непрерывной заместительной гормональной терапии 17b-эстрадиоло-эндопротезной заместительной гормональной терапии 17b-эстрадиолиин иниситисинисисиной

The aim of the study was to determine the endometrial safety of oral 17/3- oestradiol combined continuously with dydrogesterone in preventing endometrial proliferation. The low dose group comprised three 52-week (13 cycles of 28 days) studies (two of which were double blind) using a 17ft- о estradiol dose of 1 mg daily combined with dydrogesterone 2,5; 5; 10 or 20 mg daily. The high dose group comprised two 24-week double-blind studies using a 17ft-oestradiol dose of 2 mg daily combined with dydrogesterone 2,5; 5; 10 or 15 mg daily. Endometrial safety was verified by aspiration endometrial biopsies. Inadequate progestational response was defined as proliferative endometrium, endometrial polyp, hyperplasia and carcinoma. Endometrial protection was achieved with dydrogesterone at doses of 5 mg or higher combined with 1 or 2 mg 17^-oestradiol. So, 5 mg daily dydrogesterone appears to be the lowest effective dose to ensure endometrial safety in a continuous combined regimen with 1 or 2 mg 17p-oestradiol.

Continuous High-Dose (6 mg) vs. Low-Dose (3 mg) Intravitreal Ganciclovir for Cytomegalovirus Retinitis After Haploidentical Hematopoietic Stem Cell Transplantation: A Randomized Controlled Study

Purpose: To evaluate the safety and efficacy of continuous high-dose (6 mg) intravitreal ganciclovir injections (IVG) for cytomegalovirus (CMV) retinitis (CMVR) after haploidentical hematopoietic stem cell transplantation (Haplo-HSCT), and to explore factors that may influence the treatment procedure.Design: Prospective, randomized, single-blinded, positive-controlled, interventional, comparative study.Methods: A total of 22 patients with CMVR (32 eyes) were randomized to either high-dose group (IVG 6 mg weekly) or low-dose group (IVG 3 mg given twice weekly for 2 weeks as induction phase and weekly thereafter as maintenance phase). Patients who were recorded any positive CMV DNAemia or other active CMV diseases and needed systemic anti-CMV treatment during the study period were excluded. The vision outcome, variables of the treatment procedure, and incidence of complication and CMVR recurrence were analyzed and compared. Logistic regression was applied to determine the factors that may have an impact on the treatment process at baseline.Results: Compared to the low-dose group, the high-dose group resulted in a median of two less intravitreal injections (4 vs. 6 times, respectively, P = 0.016), while the rate of vision stability or improvement (81.2 vs. 87.5%), the incidence of complication (6.2 vs. 18.8%), and CMVR recurrence (12.5% vs. 6.2%) were similar (all P > 0.05). No drug-related toxicity was observed. Initial aqueous CMV-DNA load (OR: 6.872, 95% CI: 1.335–35.377, P = 0.021) and extension of lesion (OR: 0.942, 95% CI: 0.897 to .991, P = 0.020), but not dosing regimen (P = 0.162), were predictors of the treatment duration.Conclusions: Continuous high-dose regimen was well tolerated and resulted in less intravitreal injections, with similar vision outcomes and safety profiles. The clinical course of CMVR after Haplo-HSCT was determined by its own nature at baseline and could not be modified by treatment protocols under consistent immune background.

Evaluation of Intra-Articular Injection of Bevacizumab on the Prevention of Physeal Bar Formation in Type 4 Salter Harris Model in Rats: A Pilot Study

Background: This study was designed to achieve a new method as a preventive treatment for complications of growth plate fractures. In this study, we investigate the effect of intra-articular injection of anti-vascular endothelial growth factor (anti-VEGF) antibody bevacizumab on the repair process of articular cartilage in a type 4 Salter Harris injury model. Methods: A Salter Harris injury was created on the proximal tibial growth plate of 14 rats by a 1.8 mm drill. The rats were randomly classified into two groups: group LD, administration of high-dose intra-articular injection of bevacizumab (250 μg), and group HD, administration of low-dose intra-articular injection of bevacizumab (50 μg) after injury. The rats were killed 2 months postoperatively and their tibia underwent micro-computed tomography (CT) analysis, histological assessment, and measurement of tibial bone length. Results: Bony bar formation was observed in 71% of the samples in the high-dose group and in 100% of the low-dose group. Relative increase in physeal cartilage thickness (P = 0.007) and decrease in bony bar formation (P = 0.029) were observed significantly in the high dose group. There was no significant difference in tibia length between the two groups (P = 0.150). Conclusion: Intra-articular administration of bevacizumab demonstrated positive restorative effects. We suggest this method of treatment due to its potential of improving cartilage repair and capability to be used as a main or adjacent treatment in osteochondral defects.