Study of the Effect of Concurrent Therapy of Spironolactone With Levodopa on Depression Disorder in Male Rats

Background: Depression has a high prevalence and high mortality and a tremendous negative impact on people’s quality of life. This study was considered to examine the effect of levodopa and spironolactone (SPIR) in 6-hydroxydopamine (6-OHDA)-induced depression-like behavior. Methods: Parkinson was induced by the unilateral intra-nigral injection of 6-OHDA (8 µg/2 µL/rat) in the central region of the substantia nigra pars compacta (SNc). In the levodopa treatment group, 21 days after the injection of 6-OHDA, the rats were treated with (i.p.) injections of levodopa (15 mg/kg) for 14 consecutive days. In the other group, only SPIR (25 mg/kg) was added to levodopa (15 mg/kg) as a concurrent therapy according to the treatment protocol. Anxiety and depression-like behavior were assessed by behavioral tests such as passive avoidance task (PAT), open field test (OFT), tail suspension test (TST), and forced swimming test (FST). Results: Intra-nigral injection of 6-OHDA in the SNc increased anxiety and depression-like behavior. Our results showed that the use of levodopa (15 mg/kg) treatment significantly attenuated depression-like behavior induced by 6-OHDA in FST (P<0.001) and TST (P<0.001) in rats. Moreover, levodopa (15 mg/kg) + SPIR (25 mg/kg) significantly reduced the symptoms of depression-like behavior induced by 6-OHDA in OFT (P<0.05), FST (P<0.001), and TST (P<0.001) tests in rats. Conclusion: Based on the findings, the intra-nigral injection of 6-OHDA into rats could cause anxiety and depression-like behavior in the fourth week onwards. Treatment with levodopa was able to attenuate stress and depressive symptoms. Additionally, our results revealed that SPIR could improve the effect of levodopa on depression-like behavior. Base on the results of this study, it is suggested that levodopa and SPIR could have some improving effects on 6-OHDA-induced depression-like behavior in parkinsonian rats.

Case of sexually transmitted recurrent pharyngotonsillitis caused by group A streptococcus

We report a five-time recurrent pharyngotonsillitis caused by group A streptococcus (GAS) after sexual contacts and had no recurrence after concurrent therapy to both partners. Although Streptococcus pyogenes (GAS) is a Gram-positive streptococcus capable of causing a recurrent pharyngotonsillitis, the recurrent GAS pharyngotonsillitis as STI has not been published.A 30-year-old man had a high fever and sore throat. He had a repeated pharyngotonsillitis caused by GAS in spite of the sufficient antimicrobial therapy after having sex with his partner, including oral penile and oral vaginal sex. In contrast, a hug and kiss alone did not precede his episodes of pharyngotonsillitis. His partner had GAS carriage on her pharynx. He had no recurrence after concurrent therapy to both partners. The recurrent GAS pharyngotonsillitis as STI has not been published. In a patient with recurrent pharyngotonsillitis caused by GAS, the sexual history and pharyngeal carrier status of the partner should be checked.

Canine flea control: too much choice?

Ectoparasite control forms an important part of any routine canine health programme but is also an integral part of the management of pruritic skin disease in the dog. As such it is important that veterinary surgeons are aware of the life cycle of the flea and the mode of action of the numerous flea control products that are currently available. The suitability of a product may be different depending on the health status of the dog and concurrent therapy. This article considers the most important groups of flea control products.

Pembrolizumab in men with heavily treated metastatic castration-resistant prostate cancer (mCRPC).

172 Background: Pembrolizumab is approved for patients with metastatic, microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) solid tumors who have progressed on prior therapy and have no satisfactory treatment options. However, very few men with PC were included in these initial studies. We evaluated the clinical activity of pembro in a cohort of men with mCRPC and their responses based on molecular genotype. Methods: We performed a retrospective, IRB-approved review of all men with mCRPC in the Duke Cancer Center who were treated with pembro in order to define the duration of therapy, time to PSA-progression, and imaging responses according to prior/concurrent therapy and by molecular subtypes. Results: We identified 51 men who received ≥1 cycle of pembro for mCRPC. Of these, 86% (44/51) had ≥3 prior lines of therapy after ADT, including abiraterone (88%), docetaxel (86%), enzalutamide (enza, 80%), and sipuleucel-T (74%). Somatic tumor sequencing was available in 18/51 men (35%). We found that 16% (8/51) had a ≥50% confirmed PSA decline with pembro, with 8% (4/51) having ≥90% PSA decline. Two of 4 had mutations in LRP1b, one of whom also had MSH2loss and was MSI-H and TMB-high; of the other 2 patients, one had no actionable mutations and the other had no genetic testing available. Fifty-nine percent (30/51) of men were treated with concurrent therapy with pembro (most commonly enza); however, all patients with PSA responses who were concurrently treated with enza had prior documented PSA progression on enza. Overall, the median time to discontinuation of treatment was 5.8 months (mo), median PSA-PFS, defined as a 25% increase in PSA from baseline, was 1.4 mo, and median OS was 6.7 mo. Among patients with ≥50% PSA decline, duration of response ranged from 3.7 to 16.3 mo with 5 patients with ongoing responses. Conclusions: In a heavily pre-treated population of men with mCRPC, pembrolizumab was associated with a ≥50% PSA decline in 16% (8/51) of men, including a dramatic ≥90% PSA response in 8% (4/51), two of whom harbored LRP1b mutations, one also with MSH2loss and a MSI-H tumor. Large prospective studies with genomic testing are needed to identify men with the greatest chance for response to immunotherapy.