PLGA-based monolithic filaments prepared by hot-melt extrusion: In-vitro comparative study

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Diallyl sulfide alleviates cisplatin‐induced nephrotoxicity in rats via suppressing NF‐κB downstream inflammatory proteins and p53/Puma signalling pathway

Despite being a potent anticancer drug, nephrotoxicity is an adverse effect which renders the clinical use of cisplatin (Cis) limited. The protective role of diallyl sulfide (DAS); a naturally occurring organo‐sulfide, present in garlic, in cisplatin‐induced nephrotoxicity has been reported earlier. However, the mechanism through which DAS exerts its nephroprotective activity remains elusive. The aim of the current study was to elucidate the possible mechanisms underlying the reno‐protective effect of DAS in cisplatin‐induced nephrotoxicity in rats. DAS was given at 2 dose levels; 50 and 100 mg/kg, orally for 4 consecutive days, starting 1 hour after administration of single dose of cisplatin (3.5 mg/kg, intraperitoneally [i.p.]). The Cis‐induced elevation in serum urea and creatinine, degree of histopathological alterations was significantly ameliorated in cisplatin groups co‐treated with DAS. In addition, DAS significantly restored Cis‐depleted glutathione (GSH) content and superoxide dismutase (SOD) activity and attenuated Cis‐elevated Malondialdehyde (MDA) level. Also, DAS significantly reduced Cis‐increased renal expression of nuclear factor kappa B (NF‐κB) and subsequent pro‐inflammatory mediators; tumour necrosis factor alpha (TNF‐α), interleukin‐1β (IL‐1β), intercellular adhesion molecule‐1 (ICAM‐1) and inducible nitric oxide synthase (iNOS) in kidney tissues. Moreover, co‐treatment with DAS significantly inhibited Cis‐increased caspase‐8 and ‐9 levels. Additionally, DAS significantly mitigated Cis‐induced protein expression of p53, Puma, and Bax while, it significantly restored Cis‐reduced protein expression of Bcl‐xL compared to the Cis group. In conclusion, these results demonstrate that DAS ameliorates cisplatin‐induced nephrotoxicity in rats through enhancement of antioxidant defense, reduction of inflammatory cytokine tissue levels as well as inhibition of apoptosis via p53/Puma signalling pathway.     

Mucosal co-delivery of ketorolac and lidocaine using polymeric wafers for dental application

The current study aimed to investigate the effectiveness of a developed sodium alginate and polyvinylpyrrolidone K-25 (PVP K-25) polymeric wafer for the co-delivery of ketorolac and lidocaine to soft tissues for healing and pain control following gingivectomy. Nine ketorolac/lidocaine lyophilized wafers were formulated and assessed for their hydration capacity, mucoadhesion ability and in vitro release profile to select the optimum system for further clinical investigation. Wafer F6 containing 2:1 sodium alginate to PVP K-25 and 10% glycerol showed optimum properties and was selected for the clinical study. Twenty patients were included in the study and the ketorolac/lidocaine wafer was assessed versus a market product. Visual pain analog was evaluated daily for the first week and wound healing index was evaluated for one week, two weeks and one month following the procedure. The developed ketorolac/lidocaine polymeric wafer proved to be an effective method of reducing pain and discomfort together with enhancing wound healing following gingivectomy.     

Evaluation of an intervention program to prevent hospital-acquired catheter-associated urinary tract infections in an ICU in a rural Egypt hospital

Aim: Catheter associated urinary tract infections (CAUTI) are the most common hospital-acquired infection in ICUs. The aim of this study was to estimate the effectiveness of an intervention program by implementing urinary catheter bundle elements to reduce the CAUTI frequency in an ICU. Methods: The intervention study was conducted over a period of 6 months. During a pre-intervention phase, the base line catheter associated CAUTI incidence rates were determined and compared with the incidence rates during the post-intervention phase. The compliance of health care staff with urinary catheter bundle elements was also measured. The implemented CAUTI prevention bundle consisted of hand hygiene, wearing personal protective equipment, use of disposable gloves, cleansing of urethral meatus prior to catheter insertion using sterile saline, assessment of catheter need, aseptic urine sampling technique, and correct draining bag positioning.Results: During the study period, 55 out of 77 patients were diagnosed with a CAUTI. The mean CAUTI incidence rate for the pre-intervention period was 90.12/1,000 catheter days and for the post intervention phase 65.69/1,000 catheter days. The CAUTIs rate was inversely proportional to insertion bundle elements and maintenance bundle elements compliance rate. This negative relationship was statistically significant only with maintenance bundle elements (p=0.042) (r_s=–0.828). The compliance rate of the ICU nurses to the bundle elements was raised to 100% during the last 2 months of the post intervention phase.Conclusion: Increased compliance to recommended catheter associated urinary tract infections preventive practices reduced the incidence of CAUTI in an ICU unit. It is simple and effective and is recommended as a part of patient safety culture.     

Effects of TSH-suppressive therapy on cardiac morphology and function: beneficial effects of the addition of beta-blockade on diastolic dysfunction

OBJECTIVE: To investigate the effects of long-term levothyroxine (LT4) suppressive therapy on the heart and the effects of beta-blockade on cardiac functions. DESIGN: Twelve female patients receiving LT4, selected from a group of patients with TSH levels of 0.1-0.4 microU/ml, were evaluated. The control group consisted of 11 healthy subjects and 12 patients with TSH levels <0.05 microU/ml. METHODS: Cardiac evaluation consisted of a 12-lead electrocardiogram and an echocardiographic study. Left ventricular mass index (LVMI), isovolumetric relaxation time (IVR), left ventricular end systolic (LVESD) and diastolic diameters, early (VE) and late (VA) diastolic flow velocities and fractional shortening were evaluated. Exercise capacity was assessed with a bicycle ergometer. Both work load and maximal exercise time were measured. Atenolol was given to the patient group at a dosage of 50 mg/day for 3 months and evaluations were repeated. RESULTS: On basal evaluations, LVMI (96+/-17 vs 78+/-21 g/m(2)) and IVR (101+/-9 vs 91+/-4 ms) were found to be increased in the patients taking LT4 (P<0.01). LVESD was also lower than controls (P<0.05). A decrease in VE and an increase in VA were also observed in the patients (P<0.01). IVR decreased after atenolol (92+/-10 vs 101+/-9 ms, P<0.05). LVMI decreased and VE and VA improved but did not reach statistical significance after beta-blockade. Baseline work load and maximal exercise duration were significantly lower in the patients and improvements were observed after atenolol treatment. CONCLUSIONS: These results indicated that cardiac dysfunction may occur even when TSH is suppressed to 0.1-0.4 microU/ml with LT4. beta-blockade improved the cardiac functions.     

Ultrasonographic assessment of local steroid injection in Tietze's syndrome

The purpose of this study was to investigate the value of ultrasonographic examination in the diagnosis of Tietze's syndrome and assessment of the changes in costal cartilage following local steroid injection. Nine patients with Tietze's syndrome and 20 normal subjects were studied consecutively. Ultrasound examination was performed using a Sonoline SL Siemens Machine with a linear 5 MHz small parts transducer and ATL Apogee 800 with a 10 MHz linear array transducer. The affected costochondral joint was injected with a combination of 15 mg of triamcinolone hexacetonide and 1 ml of 2% lidocaine. Ultrasound examination was performed following the clinical evaluation and repeated immediately after the injection, then 1 and 4 weeks later. Abnormal echo appearance was detected as an inhomogeneous increase in the echogenicity with intense broad posterior acoustic shadow. Hypoechogenicity and a decrease in the size of costal cartilage were observed 1 week after local steroid injection with absence of the posterior acoustic shadowing. Ultrasonographic examination of costal cartilage is easy and quick to perform. We believe that ultrasound should be the screening procedure of choice for Tietze's syndrome. Local steroid injection proved to be clinically safe and effective in the treatment of patients with Tietze's syndrome.      

Time from Onset of SIRS to Antibiotic Administration and Outcomes after Subarachnoid Hemorrhage

Introduction

The interval from presentation with systemic inflammatory response syndrome (SIRS) to the start of antibiotic administration affects mortality in patients with sepsis. However, patients with subarachnoid hemorrhage (SAH) often develop SIRS directly from their brain injury, making it a less useful indicator of infection. We therefore hypothesized that SIRS would not be a suitable trigger for antibiotics in this population.

Methods

We examined the time from the development of SIRS until antibiotic initiation and its relationship to long-term neurological outcomes in patients with nontraumatic SAH. Patients’ baseline characteristics, time of antibiotic administration, and hospital course were collected from retrospective chart review. The primary outcome, 6-month functional status, was prospectively determined using blinded, structured interviews incorporating the modified Rankin Scale (mRS).

Results

Sixty-six of 70 patients with SAH during the study period had 6-month follow-up and were included in this analysis. SIRS developed in 57 patients (86 %, 95 % CI 78–95 %). In ordinal logistic regression models controlling for age and illness severity, the time from SIRS onset until antibiotic initiation was not associated with 6-month mRS scores (OR per hour, 0.994; 95 % CI 0.987–1.001).

Conclusions

In this cohort of patients with SAH, time from SIRS onset until antibiotic administration was not related to functional outcomes. Our results indicate that SIRS is nonspecific in patients with SAH, and support the safety of withholding antibiotics in those who lack additional evidence of infection or hemodynamic deterioration.