Search

Groups of four two-week-old puppies were administered serial dilutions of an intranasal vaccine containing live Bordetella bronchiseptica and canine parainfluenza virus vaccine and housed individually in isolator cages. Three vaccinated groups and one unvaccinated control group were exposed to virulent B bronchiseptica four weeks after vaccination and evaluated. Nasal swabs for bacterial culture and sera for agglutination tests were taken from all the dogs every week for four weeks. The bacteria isolated were identified by growth on specific agar and by specific PCR to distinguish between vaccine and challenge strains. The vaccine strain persisted in the nasal cavity after vaccination but no adverse reactions were observed. Serum agglutination titres were raised in the vaccinated dogs at challenge. Vaccine strains were not isolated after the challenge from most of the vaccinated dogs. The challenge strain was shed in the dogs vaccinated with the lowest dose (106.0 cfu/dose) for two to three weeks but the other vaccinated groups (107.0 and 108.0 cfu/dose) shed the challenge strain transiently or not at all. Only the group vaccinated with 106.0 cfu/dose exhibited clinical signs after challenge. [ABSTRACT FROM AUTHOR]

Abscess-forming cervical bacterial infections are rare and serious infections. Methods: We retrospectively examined the trends in abscess-forming cervical bacterial infections in children who required inpatient treatment in three periods before (January 2016 to June 2020), during (July 2020 to December 2022) and after the COVID-19 pandemic (January 2023 to June 2024). Results: The study included 96 patients with superficial cervical abscesses and 111 patients with deep cervical abscesses (34 with retropharyngeal abscesses, 51 with peritonsillar abscesses, and 26 with deep neck abscesses). Both decreased during the COVID-19 pandemic and increased significantly after the COVID-19 pandemic compared to before the COVID-19 pandemic (0.94 ± 0.92 vs. 0.50 ± 0.72 vs. 1.67 ± 1.11/month, 0.93 ± 0.96 vs. 0.60 ± 0.84 vs. 2.39 ± 1.70/month), which was related with the trends of respiratory viral infections. Bacteria were identified in 79 of the 97 cases in which punctures were performed; however, there were no significant differences between the three periods. No significant changes were found in the pharyngeal streptococcal antigen positivity rate, rate of oral antibiotic use before hospitalization, length of hospital stay, or duration of antibiotic administration before and after the COVID-19 pandemic. Conclusions: The COVID-19 pandemic has affected the epidemiology of cervical abscess-forming bacterial infections in children. Although the reemergence of respiratory viral infections after the COVID-19 pandemic may be a factor, the cause of the doubling in the number of neck abscesses after the COVID-19 pandemic remains unclear and requires further investigation.

Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors often linked to underlying genetic variants. Genetic analysis can promote gene-adjusted, specific follow-up, and surveillance protocols for both patients and their families at risk. We report the case of a 7-yr-old boy with bilateral pheochromocytoma, which recurred a year after partial adrenalectomy. The patient's father developed bilateral pheochromocytomas at 25 yr of age. Both individuals possessed a novel heterogeneous in-frame duplication germline variant of VHL , yet neither exhibited other clinical manifestations of von Hippel-Lindau disease (VHL). Traditionally, VHL missense mutations have been associated with a higher risk of PPGL development, whereas truncating mutations typically confer a lower risk. In-frame duplication variants are rarely observed in patients with VHL but may lead to changes in the three-dimensional structure of the translated protein, similar to truncating variants. Our analysis suggests that these in-frame duplications of amino acids in specific regions may cause pheochromocytomas in a manner similar to missense variants. Further accumulation of VHL cases with various genotypes and standardized open-access worldwide databases, including longitudinal and specific clinical data linked to genotypes, is required. It is crucial to consider genetic analyses for pediatricians who may diagnose childhood-onset PPGL., Competing Interests: None of the authors have any potential conflicts of interest associated with this research., (2024©The Japanese Society for Pediatric Endocrinology.)

The most common cause of persistent hypoglycemia in newborns and children is congenital hyperinsulinism (CHI). Remarkable advancements in diagnostic tools and treatments, including novel imaging and genetic techniques, and continuous subcutaneous octreotide administration, have improved the prognosis of diazoxide-unresponsive CHI; however, in clinical practice, some issues remain. Here, we report a case series consisting of four adenosine triphosphate-sensitive potassium-associated CHI cases, discuss the practical use of new international guidelines published in 2023, and suggest clinical issues associated with CHI management. Based on the clinical experience of two diffuse and two focal CHI cases, we employed an updated treatment strategy, including genetic diagnosis to determine treatment plans, careful catheter management, switching from octreotide to long-acting somatostatin, effective utilization of a continuous glucose monitoring (CGM) device, measures for feeding problems, and individualized and systematic developmental follow-up. Particularly, our cases suggest a safe method of switching from octreotide to lanreotide, elucidate the efficacy of home-based CGM monitoring, and indicate need for personalized support for feeding problems. Severe CHI is a rare and challenging disorder; thus, further accumulation of experience according to new treatment strategies is essential in generating high-quality evidence for the development and approval of new treatment options., Competing Interests: The authors declare no conflicts of interest associated with this research., (2024©The Japanese Society for Pediatric Endocrinology.)

BMP2 (bone morphogenic protein-2) is a member of the TGF-β superfamily and has essential roles in the development of multiple organs, including osteogenesis. Because of its crucial role in organ and skeletal development, Bmp2 null mice is fetal lethal. The recent report has characterized multiple patients with BMP2 haploinsufficiency, describing individuals with BMP2 sequence variants and deletions associated with short stature without endocrinological abnormalities, a recognizable craniofacial gestalt, skeletal anomalies, and congenital heart disease. However, due to a small number of reported patients with BMP2 haploinsufficiency, the genotype and phenotype correlations are not fully understood. We experienced a family of BMP2 haploinsufficiency with a novel frameshift variant NM_001200.4: c.231dup (p.Tyr78Leufs*38) which was predicted to be "pathogenic" by the American College of Genetics and Genomics (ACGM) criteria. In addition to short stature, impaired hearing ability and minor skeletal deformities, the proband exhibited isolated dextrocardia situs solitus without cardiac anomalies and abnormal locations of other visceral organs. Our study would shed light on the crucial role of BMP2 in determining the cardiac axis, and further studies are needed to assemble more cases to elucidate BMP2 role in human heart development., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

The pharmacokinetics of serum total thyroxine concentration (TT4) in euthyroid dogs was studied after concomitant administration of a levothyroxine oral solution with different types of dry diet. Mixing levothyroxine with different types of dry diet did not have any effect on TT4 pharmacokinetics in the dogs (Cmax 50.6 nmol/L, tmax 4.0 h and AUC 517 nmol h/L). This finding indicates that changing from one diet to another during levothyroxine-replacement therapy should not impact therapeutic effectiveness, and should be helpful for improvement of compliance with thyroid hormone replacement therapy in dogs treated for life with this replacement therapy., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

A series of 4-alkoxy-2-(1-piperazinyl)quinazoline derivatives was synthesized and evaluated for its ability to reverse a scopolamine-induced learned impairment in a one-trial passive avoidance task (antiamnestic activity). 2-(4-Allyl-1-piperazinyl)-4-pentyloxyquinazoline (4) showed more potent antiamnestic activity than such reference compounds as aniracetam, idebenone and bifemelane at a wide dose range (1-30 mg/kg]. Compound 4 also exhibited potent anticonvulsive and antihypoxic activities, and was selected as the most promising nootropic candidate agent.

Several types of quinazoline derivatives were prepared and examined for anticonvulsive and antihypoxic activities. Many compounds showed potent anticonvulsive activity, and their anticonvulsive profile is similar to that of phenytoin. The analysis of quantitative structure-activity relationships indicated that the anticonvulsive activity was parabolically related to the lipophilicity of the compounds. Most of the 4-alkoxyquinazolines showed potent anticonvulsive and antihypoxic activities. It is confirmed that there is a good correlation between the potencies of these activities.

A series of 4-phenoxy-2-(1-piperazinyl)quinazolines was synthesized and examined for anticonvulsive and antihypoxic activities. Many of the compounds exhibited potent anticonvulsive activity comparable to that of carbamazepine or phenytoin. Among them, 4-phenoxy-2-(4-propyl-1-piperazinyl)quinazoline (5w) was selected as the most promising candidate antiepileptic drug with few side effects. It seemed that potent anticonvulsive activity was a prerequisite for potent antihypoxic activity.

A series of 2-(4-substituted-1-(homo)piperazinyl)benzimidazoles was prepared and tested for H1-antihistaminic activity in vitro and in vivo. Most of the compounds showed antihistaminic activity and some of the 1-[2-(substituted-oxy)ethyl] derivatives exhibited potent activity. In a structure-activity comparison it was found that the oxygen atom in the 2-(substituted-oxy)ethyl group at the 1-position of the benzimidazole nucleus played an important role for potent antihistaminic activity, especially in vivo. One of the most potent compounds, 1-(2-ethoxyethyl)-2-(4-methyl-1-homopiperazinyl)benzimidazole (69), was 39 times more potent than chlorpheniramine maleate in H1-antihistaminic activity in vivo and was selected for clinical evaluation. The structure of compound 69 is of interest because it provides only a single aromatic unit linked through a chain to a basic nitrogen, while most H1-antihistaminic agents have structures that comprise a double-aromatic unit linked through a chain to a basic tertiary amino group.

With the aim of obtaining new H1-antihistaminic agents, transformations of previously reported antihistaminic benzimidazoles were performed on the basis of the concept of bioisosterism. Among the compounds prepared, imidazo[4,5-b]pyridine (8) and 4(3H)-quinazolinone (11) exhibited significant H1-antihistaminic activity.

Effects of 1-(2-ethoxyethyl)-2-(4-methyl-1-homopiperazinyl)benzimidazol e difumarate (KB-2413) on chemical mediators were investigated in vitro and in vivo. Antihistaminic activity of KB-2413 in vitro was about 2, 7 and 5 times more potent than those of chlorpheniramine, diphenhydramine and clemastine, respectively, and equipotent to that of ketotifen. This antihistaminic activity of KB-2413 was competitive antagonism to histamine. In the study preventing histamine-induced mortality in guinea pigs, the antihistaminic potency of KB-2413 (p.o.) was about 39, 780, 68 and 3 times more potent than those of chlorpheniramine, diphenhydramine, clemastine and ketotifen, respectively. In the study preventing histamine-induced increase in vascular permeability, the antihistaminic potency of KB-2413 (p.o.) was about 27 and 4 times greater than those of chlorpheniramine and ketotifen, respectively. The preventing activity of KB-2413 (i.v.) on histamine-induced increase in airway resistance was about 10 and 2 times more potent than those of chlorpheniramine and ketotifen, respectively. These results indicate that the antihistaminic potency of KB-2413 is stronger than that of chlorpheniramine and that of ketotifen which has the strongest antihistaminic activity of all reference drugs. On the other hand, KB-2413 had only very weak anticholinergic, antibradykinin and antiserotonin activity in the study in vitro or in vivo, so that KB-2413 had selective antihistaminic activity. Therapeutic index of KB-2413 calculated from the antihistaminic potency on histamine-induced mortality and acute toxicity in guinea pigs was about 110 times greater than that of chlorpheniramine.(ABSTRACT TRUNCATED AT 250 WORDS)

The metabolites of 1-(2-ethoxyethyl)-2-(hexahydro-4-methyl-1H-1,4-diazepin-1-yl)-1H-b enzimidazole difumarate (KG-2413), which has a potent H1-antihistaminic activity, were predicted on the basis of metabolic studies of related compounds and were synthesized to aid in identification of the actual metabolites and for examination of their antihistaminic activity. Among the twelve compounds prepared, nine compounds were actually found as the metabolites of KG-2413 in rat urine. The antihistaminic activities of these metabolites were found to be lower than that of KG-2413.

The quantitative structure-activity relationships (QSAR) of 2-(4-substituted-1-piperazinyl)benzimidazole derivatives for antihistaminic activity were examined. Taking into consideration the specific conformations of some derivatives, a significant correlation was obtained using Verloop's STERIMOL parameters B3 and L of the substituent at the 1-position of the benzimidazole nucleus. The results indicated that the derivatives having a substituent with a small breadth and an appropriate length at the 1-position showed potent activity. From the results, a model of the binding site is proposed. The QSAR of side effects (anticholinergic activity and central nervous system depressive effect) were also examined and the results showed that a sterically small substituent at the 1-position was required to decrease side effects.

The metabolites of 1-[bis(4-fluorophenyl)methyl]-4-(2,3,4-trimethoxybenzyl)piperazine dihydrochloride (KB-2796, 1), a cerebral vasodilator, and related compounds were synthesized to confirm the proposed structures. The structures of the metabolites (3-5) in rats were identified by means of synthesis of the authentic compounds.