Efficacy of pentamidine-loaded chitosan nanoparticles as a novel drug delivery system for Leishmania tropica

@#The present study compares the in vitro effects of nanoparticles loaded pentamidine drug and conventional pentamidine on Leishmania tropica. Herein, pentamidine-loaded chitosan nanoparticles (PTN-CNPs) have been synthesized through an ionic gelation method with sodium tripolyphosphate (TPP). Next, the physical characteristics of PTN-CNPs were determined through the surface texture, zeta potential, in vitro drug release, drug loading content (DLC), and encapsulation efficacy (EE) and compared its efficacy with free pentamidine (PTN) drug against promastigotes and axenic amastigotes forms of L. tropica in vitro. The PTN-CNPs displayed a spherical shape having a size of 88 nm, an almost negative surface charge (-3.09 mV), EE for PTN entrapment of 86%, and in vitro drug release of 92% after 36 h. In vitro antileishmanial activity of PTN-CNPs and free PTN was performed against Leishmania tropica KWH23 promastigote and axenic amastigote using 3-(4, 5- dimethylthiazol-2-yl)-2, 5-diphenyletetrazolium bromide (MTT) assay. It was observed that the effect of PTN-CNPs and free PTN on both forms of the parasite was dose and time dependent. Free PTN presented low efficacy even at higher dose (40 µg/ml) with 25.6 ± 1.3 and 26.5 ±1.4 mean viability rate of the promastigotes and axenic amastigotes, respectively after 72 hrs incubation. While PTN-CNPs showed strong antileishmanial effects on both forms of parasite with 16 ± 0.4 and 19 ± 0.7 mean viability rate at the same higher concentration (40 µg/ml) after 72 hrs incubation. Half maximal inhibitory concentration (IC50) values of PTN-CNPs toward promastigotes and amastigotes were obtained as 0.1375 µg/ml and 0.1910 µg/ml, respectively. In conclusion, PTN-CNPs effectively inhibited both forms of the L. tropica; however, its effect was more salient on promastigotes. This data indicates that the PTN-CNPs act as a target drug delivery system. However, further research is needed to support its efficacy in animal and human CL.

Measurement of antioxidant activity with trifluoperazine dihydrochloride radical cation

A novel, rapid and cost-effective trifluoperazine dihydrochloride (TFPH) decolorization assay is described for the screening of antioxidant activity. A chromogenic reaction between TFPH and potassium persulfate at low pH produces an orange-red radical cation with maximum absorption at 502 nm in its first-order derivative spectrum. TFPH was dissolved in distilled water to give a 100 mM solution. The TFPH radical cation solution was made by reacting 0.5 mL of the solution with K2S2O8 (final concentration: 0.1 mM) and diluting to 100 mL with 4 M H2SO4 solution. A linear inhibition of color production was observed with linearly increasing amounts of antioxidants, with correlation coefficients (R²) ranging from 0.999 to 0.983. The antioxidant capacity of standard solutions of an antioxidant was evaluated by comparing with the inhibition curve using Trolox as the standard. Comparison of antioxidant capacity determined with this newly developed TFPH assay and with the well-known 2,2'-azinobis-[3-ethylbenzthiazoline-6-sulfonic acid] (ABTS)-persulfate decolorization assay indicated the efficacy and sensitivity of the procedure. The proposed assay is less expensive (costs about US$4 per 100 assays) and requires only 20 min for preparation of radical cation solution in comparison with ABTS assay, in which almost 12-16 h are required for preparation of a stable ABTS radical cation solution. The present assay has the advantage over ABTS assay that it can be used to measure the antioxidant activity of the samples, which are naturally found at a pH as low as 1, because the radical cation itself has been stabilized at low pH.

Retrospective analysis of abdominal surgeries at Nepalgunj Medical College (NGMC), Nepalgunj, Nepal: 2 year's experience.

BACKGROUND: Abdominal surgeries are the commonest major operations that are performed in the department of surgery. AIM: To find out the different causes of emergency and elective abdominal surgeries at Nepalgunj Medical College Teaching Hospital (NGMCTH) Nepalgunj, Nepal. MATERIAL AND METHOD: This is a retrospective study conducted in the department of surgery at NGMCTH Nepalgunj, Nepal, over a period of 2 years (2001 to 2003). The patients included in this study were drawn from Banke, Bardiya, Kailali, Kanchanpur, Surkhet, Dang, Dailake, and Tikapur. They belong to both sexes and different age groups. All the records of these patients under went laparotomy for elective as well as emergency conditions were included in this study. The data were analyzed; tabulated and following results were obtained. RESULTS: The commonest cause of emergency laparotomies were peritonitis (peptic ulcer, enteric and appendicular perforations) whereas, the commonest cause of elective laparotomies were chronic cholecystitis with cholelithiasis followed by chronic appendicitis and pyloric obstruction. CONCLUSION: Over all, cholecystectomy for cholecystitis with cholelithiasis was the commonest operation, which was done in last two years. This disease may be because of excessive use of saturated animal fat and vegetable oil. Peritonitis was the 2nd commonest cause of abdominal surgery. Among the causes of peritonitis, peptic ulcer perforations were the frequent followed by enteric and appendicular perforations. Appendicitis was the 3rd commonest cause of abdominal surgery. Nepal, being a Hindu country, people consume excessive amount of meat, and possibly due to this, the disease of the appendix was very high as compared to other Asian countries where people live on bulk cellulose diet.

Atypical squamous cells of undetermined significance: is it worthwhile to qualify them further?

BACKGROUND: In Bethesda System of reporting cervico-vaginal smears, the equivocal epithelial cell abnormalities have been categorised as "atypical squamous and glandular cells of undetermined significance" (ASCUS and AGUS). These abnormalities may harbour minor lesions attributed to mere inflammatory changes to potentially serious high grade lesions. It is recommended to further qualify these lesions according to whether they favor a reactive or a neoplastic outcome. AIMS: We undertook the present study to assess the significance of ASCUS qualifiers. MATERIAL AND METHODS: A total of 12071 women were screened for early detection of cancer cervix. The women with ASCUS diagnosis were further qualified as ASCUS favor reactive and ASCUS favor SIL (Squamous intraepithelial lesion) according the Bethesda 1991 system of reporting. ASCUS-reactive cases were followed up by a repeat smear examination and persistent ASCUS cases were taken up for colposcopy and biopsy if indicated. All ASCUS-SIL cases were taken up for immediate colposcopy. RESULTS: The pick up rate of high grade lesions was not significantly different (P=0.47; Chi square test) on the follow up of ASCUS-reactive (2/222) and ASCUS-SIL (2/130) groups. The low grade lesions were picked up in 10/222 ASCUS-reactive and 58/130 in ASCUS-SIL, which was statistically significant (P < 0.001). CONCLUSIONS: The results of our study indicate that it is not worthwhile to qualify these lesions as majority of ASCUS-SIL also revealed only low grade epithelial which have a benign biological behaviour.

Chemo-immunotherapy and immunological study in carcinoma of larynx and laryngopharynx.

Eighteen of 25 patients had squamous cell carcinoma in the supraglottic region. Anergy to skin test antigen (DNCB) and T-cell mitogen (PHA) was observed in 17 patients with laryngeal and laryngopharyngeal malignancies. Chemo-immunotherapy did not improve the skin reactivity to either agents. However, a rise in absolute T-cell counts was observed following combined therapy. Moreover, T-lymphopenia was detected in the patient group prior to therapy as compared to mean T-cell counts in normal control subjects.

Cervical intraepithelial glandular neoplasia diagnosis and significance in relation to squamous precancerous lesions.

The endocervical epithelium of histologically confirmed dysplasia and carcinoma-in-situ cases of cervix uteri was examined for the presence or absence of intraepethelial glandular Neoplasia (CIGN). Results from 80 cases were compared with equal number of controls who were being operated for reasons other than Neoplasia. In the present communication we have used the criteria of Nuclear enlargement and elongation, hyperchromasia, stratification, increased N/C ratio, pleomorphism and dence clumping to distinguish CIGN from normal endocervical epithelial lining using the criteria mentioned above we recorded CIGN in eleven cases of test group while in two of controls which implied a statistically significant (p less than .5) association of CIGN with case series as compared to controls. Among the test group; 1, 2 (15.3%), 3 (23%) and 5 (10%) cases were associated with mild, moderate, sever dysplasia and carcinoma-in-situ respectively.