Polyphenylene carboxymethylene (PPCM), the active component of the topical contraceptive Yaso-GEL, exhibits potent antimicrobial activity against Neisseria gonorrhoeae in preclinical studies.

INTRODUCTION: Polyphenylene carboxymethylene (PPCM) is a condensation polymer that has both contraceptive and antimicrobial activity against several sexually transmitted viruses including HIV, herpes simplex virus, Ebola virus and SARS-CoV-2 in preclinical studies. PPCM, both as an active pharmaceutical ingredient (API) and in a vaginal gel formulation (Yaso-GEL), has an excellent safety profile. Here, we evaluated the efficacy of PPCM against Neisseria gonorrhoeae in vitro and in a gonorrhoea mouse model. METHODS: The minimal inhibitory concentration (MIC) of PPCM was determined against 11 N. gonorrhoeae strains by agar dilution and a microtitre plate-based method. In vivo efficacy was tested in a murine model of N. gonorrhoeae genital tract infection by applying Yaso-GEL, PPCM incorporated in 2.7% hydroxyethylcellulose (HEC), or the HEC vehicle vaginally prior to challenge with N. gonorrhoeae. Vaginal swabs were quantitatively cultured over 5 days to assess efficacy. RESULTS: PPCM MIC against N. gonorrhoeae ranged between 5-100 µg/mL (agar dilution) and 50-200 µg/mL (microtitre plate method). PPCM/HEC gel applied vaginally prior to bacterial challenge resulted in a concentration-dependent inhibition of infection. Yaso-GEL containing 4% PPCM prevented infection in 100% of mice. Incubation of N. gonorrhoeae with PPCM increased membrane permeability, suggesting PPCM directly compromises N. gonorrhoeae viability, which may be a mechanism by which PPCM inhibits N. gonorrhoeae infection. CONCLUSIONS: Yaso-GEL containing the API PPCM showed significant activity against N. gonorrhoeae in vitro and in vivo in a female mouse model. These data support further development of Yaso-GEL as an inexpensive, non-hormonal and non-systemic product with both contraceptive and antimicrobial activity against gonorrhea and other common sexually transmitted infections (STIs). Such multipurpose prevention technology products are needed by women in all economic, social and cultural circumstances to prevent unintended pregnancy and STIs.

Implications and Efficacy of Aromatase Inhibitors in Combination and Monotherapy for the Treatment of Lung Cancer.

BACKGROUND: Lung tumors express high levels of aromatase enzyme compared to surrounding normal tissue. Inhibition of aromatase has emerged as a recent therapeutic approach for the treatment of breast cancer. However, the role of aromatase inhibition in lung cancer treatment requires further investigation. METHODS: The anti-proliferative effects of aromatase inhibitors were evaluated by MTT assay. Cell migration was assessed using a wound healing assay. The mechanism of cell death was determined using the annexin VFITC/ propidium iodide staining flow cytometry method. The soft agar colony formation assay evaluated cells' capability to form colonies. RESULT: Exemestane and curcumin significantly inhibited the growth of lung cancer cell lines in a dose- and timedependent manner. The IC50 values after 48 hours of treatment with exemestane were 176, 180, and 120 µM in A549, H661, and H1299, respectively. Curcumin IC50 values after 48 hours were 80, 43, and 68 µM in A549, H661, and H1299, respectively. The combined treatment of exemestane or curcumin with cisplatin, raloxifene, and celecoxib resulted in a synergistic effect in the A549 lung cell line with a combination index of less than 1, suggesting synergism. Exemestane resulted in approximately 96% inhibition of wound closure at 100 µM, while curcumin resulted in approximately 63% inhibition of wound closure at 50 µM. Exemestane and curcumin inhibited the formation of cell colonies by reducing the number and size of formed colonies of A549, H661, and H1299 cell lines in a concentration dependent manner. Exemestane and curcumin had significantly induced apoptosis in A549 cells compared to control of untreated cells. CONCLUSION: Aromatase inhibition by exemestane or curcumin had significantly inhibited the growth of lung cancer cell lines, synergized with cisplatin, raloxifene, and celecoxib, suppressed lung cancer cell migratory potential, induced apoptosis, and reduced colony formation of lung cancer cells.

Microbiological and Antibiotic Sensitivity Profile of Postoperative Endophthalmitis in a Tertiary Eye Care Hospital of North India.

INTRODUCTION: We describe the microbiological profile of postoperative endophthalmitis from northern India and analyse the pattern of antibiotic sensitivity which may have changed due to development of resistance secondary to overuse of antimicrobial drugs. MATERIALS AND METHODS: This is a retrospective study of postoperative endophthalmitis from January 2011 to December 2017 in a tertiary eye hospital of northern India. Any patient developing endophthalmitis within one year of any intraocular procedure was included in the study. According to severity, treatment with a trial of intravitreal antibiotic injections or core vitrectomy was decided. Ocular samples were collected which were either anterior chamber tap or vitreous biopsy and sent for microbiological examination. The samples were stained with Gram's and KOH stain and cultured on chocolate agar, blood agar, brain heart infusion broth and Sabouraud dextrose agar. RESULTS: A total of 545 patients of postoperative endophthalmitis were analysed which showed a male predilection (60.5%) with maximum patients between the age group 50-69 years. 292 patients (53.5%) were culture negative and 253 patients (46.4%) were culture positive. Most common organism identified was Staphylococcus in 73 patients followed by Pseudomonas in 48 patients. Staphylococcus species was most sensitive to vancomycin (97%) followed by amikacin (91%) followed by gentamicin and moxifloxacin (88% each). Pseudomonas was the second most common isolate which showed maximum sensitivity to imipenem (82%) followed by ciprofloxacin(60%). Polymicrobial infection was noted in 23 patients. The most common fungal isolate was aspergillus in 11 patients, followed by fusarium in 10 patients. CONCLUSION: Our study shows that gram positive bacteria are the most common organisms in postoperative endophthalmitis and are most sensitive to vancomycin, followed by gram negative bacteria which show increased sensitivity with imipenem than commonly used antibiotic - ceftazidime.

Efeitos do agarol e do trigliceril sobre a cicatrizaçäo de pele: estudo experimental em ratos / Effects of agarol and trigliceril; on cutaneous wound healing: experimental study in rats

Desde os mais remotos tempos pesquisam-se incessantemente drogas que acelerem o processo cicatricial normal. No Hospital de Clínicas de UFPr preconiza-se a limpeza de feridas limpas com soluçao salina de NaCl a 0,9 por cento. Alguns serviços têm utilizado empiricamente o Agarolr e o Triglicerilr na confecçao do curativo após este procedimento. Este estudo objetivou avaliar experimentalmente a evoluçao de feridas cutâneas, em ratos, produzidas por incisao cirúrgica tratadas com soluçao de NaCl a 0,9 por cento, Agarolr e Triglicerilr. Utilizou-se 24 ratos, divididos em três grupos: C, controle, submetido à troca diária de curativo após limpeza com soluçao de NaCl a 0,9 por cento; grupo A com aplicaçao de Agarolr e grupo T com aplicaçao de Triglicerilr. Verificou-se que no terceiro e décimo quarto dias de pós-operatório o Agarolr e o Triglicerilr nao influenciaram o processo cicatricial. No sétimo dia de pós-operatório verificou-se houve aumento da quantidade de tecido de granulaçao nos grupos tratados com Agarolr e diminuiçao da neovascularizaçao no grupo Triglicerilr.

Estudo comparativo do ágar com a soluçäo salina isotônica no tratamento de feridas infectadas, em cobaias / A comparative study using agar and isotonic saline solution in the treatment of infected wounds, in guinea pigs

Recentemente os hidrogéis tem sido investigados no sentido de manterem a umidade das feridas e assim facilitarem a cicatrizaçäo. Este estudo tem por objetivo comparar, macroscópica e bacteriologicamente, os efeitos do ágar com os da soluçäo salina isotônica em feridas infectadas. Foram utilizadas 32 cobais. As bactérias usadas foram Staphylococcus aureus. Foi realizada a incisäo com 2 cm de extensäo e 1 cm de profundidade. Foi inoculado 1 ml da soluçäo no tecido subcutâneo, e 1 ml na regiäo central da mesma, foi imediatamente suturada com pontos de "Prolene 2-0". No 5§ dia, os animais foram aleatoriamente divididos em 2 grupos. Concluiu-se que em cobaia, a cicatrizaçäo de feridas infectadas com Staphylococcus aureus e tratadas com Agarol, processou-se, mais eficientemente do que as tratadas com soluçäo salina Isotônica

Agar dilution method for susceptibility testing of Neisseria gonorrhoeae

The antibiotic susceptibilities of Neisseria gonorrhoeae isolates obtained from patients attending a clinic for sexually transmitted diseases in Tucuman, Argentina, were determined by the agar dilution method (MIC). 3.5 per cent of the isolates produced ß-lactamase. A total of 96.5 per cent of ß-lactamase negative isolates tested were susceptible to penicilin (MICó2 µgml-1); 14.03 per cent of the tested isolates were resistant to tetracycline (MICó 2 µgml-1), and 98 per cent of the tested isolates were susceptible to spectinomycin (MICó 64 µgml-1). The MICs for 95 per cent of the isolates, tested for other drugs were: ó µgml-1 for cefoxitin, ó0.06 µgml-1 for cefotaxime, ó0.25 µgml-1 for norfloxacin, ó 10 µgml-1 for cephaloridine, ó 10 µgml-1 for cephalexin and ó50 µgml-1 for kanamycin. Antibiotic resistance among N.gonorrhoeae isolates from Tucuman, Argentina, appeared to be primarily limited to penicilin and tetracycline, which has been a general use against gonorrhoeae in Tucuman since 1960. Periodic monitoring of the underlying susceptibility profiles of the N.gonorrhoeae strains prevalent in areas of frequent transmission may provide clues regarding treatment options and emerging of drug resistance.