Activity and interactions of antibiotic and phytochemical combinations against Pseudomonas aeruginosa in vitro

In this study the in vitro activities of seven antibiotics (ciprofloxacin, ceftazidime, tetracycline, trimethoprim, sulfamethoxazole, polymyxin B and piperacillin) and six phytochemicals (protocatechuic acid, gallic acid, ellagic acid, rutin, berberine and myricetin) against five P. aeruginosa isolates, alone and in combination are evaluated. All the phytochemicals under investigation demonstrate potential inhibitory activity against P. aeruginosa. The combinations of sulfamethoxazole plus protocatechuic acid, sulfamethoxazole plus ellagic acid, sulfamethoxazole plus gallic acid and tetracycline plus gallic acid show synergistic mode of interaction. However, the combinations of sulfamethoxazole plus myricetin shows synergism for three strains (PA01, DB5218 and DR3062). The synergistic combinations are further evaluated for their bactericidal activity against P. aeruginosa ATCC strain using time-kill method. Sub-inhibitory dose responses of antibiotics and phytochemicals individually and in combination are presented along with their interaction network to suggest on the mechanism of action and potential targets for the phytochemicals under investigation. The identified synergistic combinations can be of potent therapeutic value against P. aeruginosa infections. These findings have potential implications in delaying the development of resistance as the antibacterial effect is achieved with lower concentrations of both drugs (antibiotics and phytochemicals)

DEVELOPMENT OF MICRO-PATTERNED FILMS FOR OPHTHALMIC DRUG DELIVERY

Ocular inflammation is commonly associated with multiple eye disorders such as microbial infections, allergies and post-operative healing. Topical anti-inflammatory agents delivered via eye drops or ointments are commonly used for the management of inflammation. These treatment regimens involve high dosing frequency over prolonged periods depending on the severity of inflammation. Further, only 5% of administered drug may be available for action due to the physiological barriers of the eye and formulation losses. Collectively, this reduces patient compliance and causes irregularity in drug exposure. Therefore, there is a need for prolonged residence time of formulation in the eye to achieve sustained drug delivery. Mucoadhesive polymers and ocular inserts have been used for this purpose. Additionally, topographical features have been explored to enhance adhesion to mucosal surfaces. Taking inspiration from these approaches, we hypothesized that micropatterned polymeric films will prolong residence time by enhancing interactions with ocular mucosal surface and sustain the drug release. We developed micropatterned films containing a hydrophobic drug, hydrocortisone (HCT) or a hydrophilic drug, olopatadine hydrochloride (OLO) using GRAS-compliant cellulose-based polymers and polylactic-co-glycolic acid (PLGA). Films with 100 µm sized square, triangle and circle micropatterns were manufactured and characterized for HCT / OLO release. We demonstrated an in vitro sustained release for up to 72 hours, for both HCT and OLO. The shape of micropatterns did not impact drug release, however, PLGA and hydroxyethylcellulose impacted release of HCT and OLO, respectively. Tensile properties of films were dependent on the film composition and not micropatterns. A novel method to investigate the mucoadhesion potential of micropatterned films was developed. For cellulose and PLGA-based films, micropatterns did not improve adhesion to porcine intestinal tissue. Collectively, our results suggest that sustained release of anti-inflammatory drugs can be achieved by using cellulose and PLGA-based films and the presence of 100 µm sized micropatterns did not improve adhesion to mucosal surface. Further optimization of formulation and micropattern characteristics will be required to maximize sustained release and mucoadhesion in films, which can potentially be used for long-term delivery to the anterior region of the eye

Functional outcome analysis of fixation of distal radius fractures using five pin technique

Background: One of the most frequent injuries seen in orthopaedic practise is a distal radius fracture. They account for 8-15% of all adult bone injuries. Younger and older age groups are both affected by distal radius fractures, which are bimodal in distribution and correspond to high and low energy trauma, respectively.Methods: 25 patients with distal radius fractures who were hospitalised and subsequently underwent five pin fixations as well as those who came to the outpatient department for postoperative follow-up.Results: We evaluated at 25 patients who had distal radius fractures prospectively. The patients' ages ranged from 22 years to 68 years old, with a mean age of 42.8 years among them at the time the fracture was first noticed. Among the patients, there were 18 men (72%) and 7 women (28%).Conclusions: The five-pin technique treats displaced intra and extra articular fractures without significant articular and metaphyseal comminution and is minimally invasive

Therapeutic Implications of Targeting Energy Metabolism in Breast Cancer

PPARs are ligand activated transcription factors. PPAR agonists have been reported as a new and potentially efficacious treatment of inflammation, diabetes, obesity, cancer, AD, and schizophrenia. Since cancer cells show dysregulation of glycolysis they are potentially manageable through changes in metabolic environment. Interestingly, several of the genes involved in maintaining the metabolic environment and the central energy generation pathway are regulated or predicted to be regulated by PPAR . The use of synthetic PPAR ligands as drugs and their recent withdrawal/restricted usage highlight the lack of understanding of the molecular basis of these drugs, their off-target effects, and their network. These data further underscores the complexity of nuclear receptor signalling mechanisms. This paper will discuss the function and role of PPAR in energy metabolism and cancer biology in general and its emergence as a promising therapeutic target in breast cancer

Safety and efficacy of topical tranexamic acid over intravenous tranexamic acid in reducing blood loss and transfusion rates in hip and knee arthroplasty

Background: Tranexamic acid (TXA) is increasingly used in orthopedic surgery to reduce blood loss. Hence the present study was undertaken to compare the efficacy of topical TXA and intravenous (IV) TXA in reducing blood loss and transfusion rate in primary total hip and total knee arthroplasty.Methods: Total of 31 cases undergoing either primary THA (23 cases) or TKA (8 cases) during a study period from June were enrolled. Outcome measures were drained output, transfusion rate, drop in haemoglobin (Hb) and blood loss measured by Nadler et al formula.Results: In THR group, 12 (52.17%) cases and in TKA group, 3 (37.5%) cases were managed using IV TXA whereas 11 (47.82%) and 5 (62.5%) cases were managed using topical TXA in THR and TKR group respectively. The mean drain output was greater among IV TKR group (261.66±129.60 ml) as compared to topical TKR group (210±129.49 ml). In THR drain output in IV group was 216±104.08 ml. In both the groups, mean blood loss was lower in cases where IV TXA was administered as compared to topical TXA, (p>0.05). The mean drop in Hb was greater after topical administration of TXA in both the groups as compared to IV administered TXA. In THR group, 9 (39.13%) patients required blood transfusion. In sickle cell disease patients, we found more blood loss and drain output as compared to non-sickle cell disease (SCD) patients.Conclusions: Both IV and topical TXA are clinically effective and safe in decreasing calculated blood loss, Hb drop after THA and TKA.

Comparison of functional outcomes and complications of conservative management verses surgical fixation with a locking compression plate in the treatment of displaced middle third clavicular fracture

Background: About 3 to 5 percent of all fractures are clavicle fractures, which account for 45 percent of fractures at the shoulder. While fractures of the lateral and medial thirds of the clavicle account for 15% and 5% of all clavicle fractures, respectively, middle third fractures account for 80% of all clavicle fractures.Methods: patients were divided into two groups at random. Patients selected for conservative treatment with figure of eight Clavicle Brace and arm sling/pouch were treated with the brace immediately and for surgical intervention with locking plating. Constant and Murley's scoring system was used to check for signs of healing and functional improvementResults: The 40 patients in the current study include 20 with a new fracture of the mid-third clavicle who underwent surgical treatment with clavicular locking compression plate and screws and 20 who underwent conservative treatment with a figure-eight clavicle brace and arm pouch/sling. There was a statistically significant difference in the Constant and Murley score between the surgical group and the conservative group.Conclusions: According to the present study, patients with a displaced mid-third clavicle fracture may benefit more from surgery than from conservative treatment.