Simvastatin Solid Lipid Nanoparticles for Oral Delivery: Formulation Development and In vivo Evaluation.

Solid lipid nanoparticles have been increasingly utilised for improving oral bioavailability of drugs. Simvastatin is biopharmaceutical class 2 drug with poor oral bioavailability of 5%. In the present study, simvastatin solid lipid nanoparticles were successfully prepared by hot melt emulsification process and optimised with respect to surfactant and lipid concentration, and drug loading. The nanoparticles were characterised for entrapment efficiency, particle size, morphology, crystallinity and thermal behavior. Optimised formulations prepared from solid lipids glyceryl behenate and glyceryl palmitostearate containing Tween 80 as surfactant exhibited satisfactory entrapment efficiencies above 96% and mean particle size below 200 nm. The electron micrographs indicated that lipid nanocarriers were almost spherical in appearance. X-ray diffraction and differential calorimetric studies proved that the drug was amorphised in the lipid matrix and did not crystallise out. To improve the physical as well as chemical stability of formulations, dry adsorbed nanoparticles were prepared by evaporative drying method using a carrier. The adsorbed nanoparticles demonstrated good flow properties and satisfactory reconstitution properties. Pharmacodynamic studies of simvastatin solid lipid nanoparticles revealed improved reduction in total cholesterol values as compared to pure drug powder indicating improved bioavailability.

Perspectives on medicinal properties of mangiferin.

Mango tree, Mangifera indica, has been cultivated in India and several other tropical countries for centuries, and it is a good source of compound 'mangiferin'. Mangiferin's xanthonoid structure with C-glucosyl linkage and polyhydroxy component is believed to be crucial for its free radical-scavenging ability leading to a potent antioxidant effect. A number of biological activities of mangiferin have been suggested, including antidiabetic and antiinflammatory abilities. These might be explained by its antioxidant ability as well as its ability to modulate several key inflammatory pathways. Mangiferin has also been shown to be an effective inhibitor of NF-κB signaling pathway. This partially explains its antiinflammatory ability and, additionally, points towards its anticancer potential. The anticancer effects of this compound are just beginning to emerge, and in this comprehensive review, we provide information on what we know about the chemistry and biological effects of mangiferin, which would likely create interest among researchers to design further mechanistic studies in order to better understand and exploit the biological activities of this compound.

Stability Indicating RP-HPLC Method for Simultaneous Determination of Simvastatin and Ezetimibe from Tablet Dosage Form.

A simple, specific and sensitive reverse phase high performance liquid chromatographic method was developed and validated for simultaneous determination of ezetimibe and simvastatin from pharmaceutical dosage forms. The method uses C18 ODS Hypersil column and isocratic elution. The mobile phase composed of acetonitrile:phosphate buffer (pH 4.5, 0.01M) in the ratio of 65:35 v/v was used at a flow rate of 1.0 ml /min. UV detector was programmed at 232 nm for first 10 min and at 238 nm for 10 to 20 min. All the validation parameters were in acceptable range. The developed method was effectively applied to quantitate amount of ezetimibe and simvastatin from tablets. The method was also applied suitably for determining the degradation products of ezetimibe and simvastatin.

Bacteriuria and urinary retention following gynaecological surgery: comparing short vs long term catheterization.

BACKGROUND: Post operative bladder drainage is important care following gynaecological surgeries. This study was done to compare the incidence of urinary retention and bacteriuria following long term versus short term catheterization. METHODS: The patients who were admitted for gynaecological major surgeries were enrolled in this study. One group of patients had post operative indwelling catheterization for 24 hrs (short term catheterization) and another group of patients had catheterization for more than 48 hrs (long term catheterization). The urine examination and culture sensitivity was sent for all patients at the removal of catheter. The patients were followed after removal of catheter for urinary retention. RESULTS: Total of 102 patients were studied. There were 48 patients in short term catheterization group and 54 patients in long term catheterization group. In short term catheterization group, 3 (6.2%) cases had bacteriuria and no cases of urinary retention were observed. In prolonged catheterization group, 6 cases (11.1%) had bacteriuria and 2 cases (3.7%) had urinary retention. CONCLUSIONS: This study has concluded that short time catheterization following gynaecological surgery had fewer incidences of bacteriuria and urinary retention than long term catheterization.

Indication for labour induction and predictors for failed induction at KMCTH.

OBJECTIVE: To study the incidence and indications for labour induction and study the predictors of failed induction. MATERIAL AND METHOD: A hospital based prospective study done over a 12 month period between 1st November 2007 to 30th October 2008. SELECTION CRITERIA: Singleton pregnancies beyond 37 weeks with vertex presentation and unscarred uterus requiring induction of labour. RESULTS: The incidence of labour induction was 19.7%. Operative delivery was 34.6% in the study group and 27.4% in those with spontaneous onset of labour. 74.07% of the induction group required operative delivery for failed induction and 25.03% for foetal distress. The predominant indication for induction was post term pregnancy (51.28%) followed by PROM (17.3%), isolated oligohydramnios (8.97%), hypertensive disorders of pregnancy (8.33%), maternal perception of decreased foetal movements (7.69%) and others. Failed induction was higher in nulliparas (41.2%) as compared to multiparas (23.7%). Failure rate was 53.8% when maternal age >30 y and 28.2% in those <30 y. Women with normal BMI had a failure rate of 25.6% compared to 36% for overweight and 44.4% for obese women. 24.1% had failed induction when Bishop score was >5 and 40.8% when Bishop score was <5. Between 38-41 weeks pregnancy failed induction occurred in 28-31% while it was higher at <38 weeks and >41 weeks pregnancy. The best outcome was seen when the birth weight was 2500-2900 g (22.5% failures) while 72.7% had failed induction when the birth weight was >3500 g. The duration of induction was >24 hours in 42.6% of women and 48.2% were in the latent phase of labour when taken for caesarean section. CONCLUSION: Despite the proven benefit of induction of labour in selected cases, one must keep in mind its impact on increasing the rates of operative delivery. Strategies for developing practice guidelines may help to prevent unwarranted case selection and help to reduce the current high operative delivery rates.

A study of Body Mass Index (BMI) of Nepalese women attending gynaecology clinic.

This prospective study was carried out to find out the body mass index (BMI) of all the women attending a gynaecological clinic at Kathmandu Valley. Total of 1450 women attended this clinic over the study period. After excluding few hundreds of women, one thousand women of reproductive age (15-49) were enrolled. Detail history was taken, general, systemic and pelvic examinations were performed and a provisional diagnosis was made on the clinical ground. In this process height and weight of each patient was measured then Body Mass Index (BMI) was calculated. Eight percent (8%) of women were underweight and equal numbers of them were obese too. Forty-four point six percent were healthy and 37.3 were overweight. Most of them were diagnosed vaginitis, urinary tract infection (UTI), pelvic inflammatory disease (PID), subfertility, menstrual disorders, and cervical conditions. In eleven percent no gynaecological abnormalities were detected (NAD). Commonly diagnosed conditions were vaginitis, UTI, PID, primary subfertility and menstrual disorders were the commonly diagnosed conditions.

Rupture uterus in primigravida: morbidity and mortality.

OBJECTIVE: This paper is aimed to present "Rupture of the uterus (RU) in primigravida "- unscarred cases which are supposed to be extremely rare. MATERIAL AND METHOD: The charts of patients labelled as "Rupture Uterus" for the period 1985 - 2005 AD (2042 - 2061 BS), 20 years were taken out and analysed. RESULT: There were 251 cases of rupture uterus during the study period giving the incidence of 0.09% i.e. 1:1100 among live births in a very busy tertiary maternity hospital of capital, Kathmandu of Nepal. There were 60% spontaneous, 29% scar dehiscence and 11% Iatrogenic/traumatic rupture and death due to RU was 7.9%(n=20). Fifteen cases (6%) were primigravid patients -- six were young primi (age 19 and below) and 9 primigravid patients. Five cases were referred from the district hospitals. Ten cases were brought from very far off i.e. more than 50 KM from the city. One case presented at 34, one at 41 and all the others presented between 38 to 40 weeks of gestational age. Only three cases had attended ante-natal clinics. All were having labour pain for more than 48 hours at home. Findings of laparotomy: The lesions found were: ruptured bladder and complete lower segment (CLS) up to the cervix - 1, CLS & cervix -2, complete lower segment (CLS) 1, Complete upper segment (CUS) - 2, Complete upper & lower segment (CULS) - 6, (one had tear at posterior wall of the uterus and the other had tear up to posterior vaginal wall) and Incomplete lower segment (LS) 2. Blood grouping & Rh: six cases had O+, four had A+, four had AB+ and one had B positive. The blood transfusion given was 1 - 4 units. The treatment given was laparotomy and repair in 10; one had LUSCS, repair of bladder and cervical injury. One had repair and bilateral tubal-ligation, one had subtotal hysterectomy and another had hysterectomy & repair of posterior wall of vagina. Four cases were admitted in the state of shock among which 1 had irreversible shock and died before surgical intervention. Another died on the 3rd post-operative day due to convulsions and shock. Maternal mortality (MM) was 13% (2/15) in primips. All cases presented with intrauterine fetal death (IUFD) and had still births (one baby was hydrocephalic). The hospital stay varied from 3 - 170 days. Four cases had vesico-vaginal fistula (VVF) CONCLUSION: Rupture of uterus in primigravida though rare, has been common in developing countries with low socio-economic status.

Antiproliferative activities of iron and platinum conjugates of salicylaldehyde semi-/thiosemicarbazones against C6 glioma cells.

The identification of novel therapeutic agents for the management of malignant gliomas represents an area of active research. Here, we show that among the iron and platinum complexes of 2-hydroxybenzaldehyde semi-/thiosemicarbazones the latter inhibits the growth of C6 glioma cells in vitro with an IC50 value of 45 microM. Structural characterization reveals iron complexes to be octahedral having intermediate S = 3/2 spin states while platinum complexes are found to be square planar moieties. Our findings suggest that the platinum compounds of 2-hydroxybenzaldehyde thiosemicarbazone are potential candidates for the treatment of malignant gliomas.

Rupture of the pregnant uterus--a 20 year review.

UNLABELLED: Nepal is a land-locked developing country located in between China and India with a population of 2.34 millions. The male: female ratio being 49:51 and very high maternal mortality. (539/100,000 live birth-1996) The geography of the country makes the situation very much divergent and difficult to cater the health services, especially operative procedures in remote places. THE AIMS OF THE STUDY ARE:- 1. To find out the incidence of R.U, distance from where the patients came, age, parity antenatal attendance, type of rupture, type of intervention and foetal outcome. 2. To suggest the concerned authorities to focus their attention to strengthen and expand comprehensive emergency obstetric care service (CEOCS) in remote areas of the country. MATERIAL AND METHOD: This is a retrospective study of rupture of pregnant uterus (RU) after 28 weeks of pregnancy for the period of 20 years from 1985 to 2005 A.D. (2042-2061 BS) admitted in the very busy tertiary centre for women (Maternity Hospital, Thapathali, Kathmandu.) with approximately 16000 deliveries and 11% Caesarean section rate per year. Available charts from hospital records of cases of R.U. admitted for the period of 20 years were analysed. During the period, 251 cases of R.U. were admitted. RESULT: There were 272245 live births, 25819 Caesarean section, 270 maternal deaths and 11197 perinatal foetal deaths, during the study period. Incidence of rupture of pregnant uterus was (0.09%) 1:1100 live-birth. There were 60% spontaneous, 29% scar rupture and 11% traumatic rupture. Maximum cases were brought from distance of more than 70 kilometres away, between 25-29 years of age, (mean age 28.7), of third and fourth gravida at 36-40 weeks of gestational period with 68% without antenatal attendance. Seventy percent (70%) had complete rupture. Sixty percent (60%) were managed with suture repair with bilateral tubal ligation, 24% had only repair and 15% had hysterectomy. The case mortality of R.U. (n=20) was 7.9%. Two percent (n=5) cases died before intervention due to arrival in moribund condition. Seventy five percent (75%) cases had stillborn babies. Conclusion More cases of RU are coming to the hospital due to better communication and awareness of the people outside the capital, and case- mortality is reduced compared to previous years.

A profile of menstrual disorders in a private set up.

Menstruation and its disorders are still considered unholy and impure and are not yet recognised as significant reproductive health morbidity. Therefore a prospective study was carried out at a private clinic for a period of three months where total number of patients coming with current or past menstrual problems are 525. This number did not include pregnant women or those on any hormonal medications or having dysfunctional uterine bleeding. This study aimed to find out the incidence of Menstrual Morbidity and their mode of presentation. It has also tried to find out these women's age, parity, age of menarche and number, following discriminating traditional rituals during their 1st and regular menses, their family planning status and the districts from where they came to Kathmandu for their treatment. In this study, menstrual morbidity was found to be 43.75%. Approximately 60% of women having menstrual complaints had absolutely normal menstrual cycle; whereas 13% of them had irregular, 17% of them had prolonged and 6% had short menstrual cycle. A significant number (46%) of women although suffering from menstrual problems presented with other symptoms like vaginal discharge, pain lower abdomen, subfertility, urinary problems, abdominal lumps and for cuT check-ups. 3% of the women who presented with vague, non-specific complaints asking for a general check up had one or the other menstrual problem. Although approximately 69% of these women were from the age group of 20-39 years, 4% of them were adolescents and 27% above 40 years. It was observed that although approximately 78% of these women were primi- and multiparous ladies, 22% were unmarried and nulliparous suffering from various menstrual morbidities. More than 55% of these women had their menarche at the age of 12-14 years. It was not surprising to note that more than 90% of women had to follow the traditional unhealthy and unsociable rituals during their first menstruation. More than 75% of them had to follow the discriminating traditional rituals which consider a menstruating woman untouchable for 5 days of every month throughout their active reproductive lives. 20% of these women were using non-hormonal contraceptive methods, out of which more than 50% had undergone permanent sterilisation. It was a matter of pride to note that this clinic was providing the health care services to the adolescents and women of 13 zones and more than 52 districts of the country.

Hysterectomy: an analysis of perioperative and post operative complication.

OBJECTIVE: To document peri operative and post operative complication observed after hysterectomy, regardless of route on the operator. MATERIAL AND METHODS: A hospital based prospective study was carried out in department of obstetrics and gynaecology, KMCTH Sinamangal for six months. The study was carried out in patients undergoing hysterectomy who were followed from the time of admission to the time of discharge and two weeks thereafter. And followings were noted--Indication; route of hysterectomy, intraoperative and postoperative morbidities during hospital stay and after two weeks of discharge was noted. RESULT: Total number of hysterectomy carried out was 50. 31 (62%) were Total abdominal hysterectomy, and 19 (38%) were vaginal hysterectomy. Indication for total abdominal hysterectomy were fibroid uterus 12 (24%), DUB 8 (16%), CIN 4 (8%), chronic cervicitis 1 (2%). II U-V prolapse with previous LSCS 1 (2%), endometriosis 1 (2%). Prophylactic for Ca breast 1 (2%), Postmenopausal bleeding 1 (2%). All cases of vaginal hysterectomy were performed for 2nd degree U-V prolapse. Intra operative complication during surgery were two cases of haemorrhage (4%) each in both total abdominal hysterectomy and vaginal hysterectomy. There was one case of bladder injury during abdominal hysterectomy. Postoperative complication noted were febrile morbidity 1 (2%) in abdominal hysterectomy. Urinary tract infection remains the single most common febrile morbidity. There was one case of secondary haemorrhage in both type of hysterectomy. One was managed conservatively and other required laparotomy. There were three (6%) cases of wound infection in abdominal hysterectomy of two which were sanguineous discharge and one was frank pus which required secondary suture.

"Brought Dead" - cases of maternal mortality.

Seven cases that were brought dead on the way to the hospital in 2057 BS (2000-2001 AD) have been presented in this study. Among seven, two cases were young primiparas, one was a grand multipara and four were between ages 20-25 years. Of these, one had post abortion complications, two were complicated by non-delivery and four had third stage complications. The information that the patient was dead on arrival to the hospital was received by the attendants in all cases with shock and disbelief so that it was very difficult to take proper history. An important point noted by this study was that only four maternal deaths occurred in the hospital and were recorded in the hospital statistics in that year, so that the number of deaths that occurred in transit to the hospital and were technically excluded from the hospital statistics exceeded the number of maternal deaths recorded in the hospital statistics. Another interesting point was that none of the seven women who expired on the way to the hospital were living at a distance greater than 15 Km from the hospital and yet had not attended antenatal clinic, implying that inadequate use of health services even in areas with relatively easy access to proper heath care is a major contributor to maternal death.

Case of xeroderma pigmentosum with well differentiated squamous cell carcinoma in the eye.

A seven year old female child presented with complaints of increased freckling over the face since the age of two years and a rapidly growing mass over the right eye. She underwent excisional biopsy of the mass over the eye which on histopathological examination was diagnosed as squamous cell carcinoma.

Chemical probes for water-oxidation: synthetic manganese complexes in photoactivation of water splitting complex and as exogenous electron donors to photosystem II.

Photoactivation of the water splitting enzyme was performed with 13 different synthetic manganese complexes and characterized by oxygen evolution yield, thermoluminescence and chlorophyll fluorescence induction kinetics. The efficiency of different compounds in photoactivation correlated with the rate of linear electron transport in the presence of these compounds. The organic ligands, associated with the manganese ions, do not prevent the photoactivation of the water splitting complex (WOC). Photoactivation with different manganese complexes depended on the number of the Mn-ions in the complex, their valence state and the nature of their donor atoms. The most efficient restorations were achieved by using tetrameric complexes having a dimer+dimer structure, complexes containing Mn(II) ions, and having 4-6 oxygen and 0-2 nitrogen atoms as donor atoms. Further, the effectiveness of photoactivation depended largely on the structure of the complexes. Our data support the notion that WOC in intact thylakoids requires the cooperation and well determined arrangement of all four manganese ions, and argue against the hypothesis that two manganese ions are sufficient for water splitting. Photoactivation by some complexes led to anomalous flash-oxygen patterns, which are explained by a modified/perturbed water splitting complex.

A disposable optrode using immobilized tyrosinase films.

A disposable fiber-optic sensor based on the immobilized tyrosinase enzyme in a composite biopolymer and its application for the detection of 3,4-dihydroxyphenyalanine (L-dopa) and its analog are described. The enzymatic oxidation product of L-dopa was stabilized through formation of an adduct with 3-methyl-2-benzothiazoline hydrazone resulting in enhanced accuracy and sensitivity of the measurements. The response was found to be linear and concentration dependent in the range of 5 x 10(-5) to 4 x 10(-4) M (r(2) = 0.9307) for the substrate l-dopa over the pH range 5.8 to 7.2 with response times of 8 min. The immobilized enzyme films are stable for 4 months when stored under moisture-free conditions at 4 degrees C.

An optical biosensor employing tiron-immobilised polypyrrole films for estimating monophenolase activity in apple juice.

A method is described for the incorporation of tiron as a substrate for tyrosinase enzyme into a polypyrrole film deposited on indium titanium oxide (ITO) glass. The presence of tiron in the polypyrrole film is verified by cyclic voltammetry (CV). The enzyme activity using the polypyrrole-tiron film is confirmed by the catalytic conversion of immobilised substrate to quinones by the enzyme. The use of both potentiometric and optical methods for the detection of the catalytic activity of the polypyrrole-tiron film and their potential use for the determination of monophenolase activity of apple polyphenol oxidase is described. This is the first report of this kind whereby tiron has been immobilised in a polypyrrole matrix for the enzyme activity determination.

Targeting Estrogen Receptor Sites in Human Breast Cancer Cell Line T47D With Copper Conjugates of Nonsteriodal Anti-inflammatory Drug Derivatives: Antiproliferative Activity of Ketoprofen Derivative and its Copper Complex.

A square planar copper complex of derivatized NSAID drug (Ketoprofen thiosemicarbazone [3-benzoyl-alpha-methyl benzene acetic acid thiosemicarbazone]), is characterized by elemental analysis, spectroscopy, electrochemistry and magnetic susceptibility studies which exhibits dose-dependent and enhanced antiproliferative effects on human breast cancer cell line T47D rich in progesterone receptors.

Enhanced antioxidant activities of metal conjugates of curcumin derivatives.

Antioxidant properties of three Curcumin derivatives in which the 1,3-diketone system is appended with nitrogen and sulfur donors and their copper conjugates are examined for the first time. Metal conjugation seems to offer distinct advantages in radical scavenging activities of curcumin compounds.

Hydroxynaphthoquinone metal complexes as antitumor agents x: synthesis, structure, spectroscopy and in vitro antitumor activity of 3-methyl-phenylazo lawsone derivatives and their metal complexes against human breast cancer cell line mcf-7.

The C-3 substituted phenylazo derivatives of lawsone (2-hydroxy-l,4 p-naphthoquinone, III) were synthesized and characterized. The X-ray crystal structure was determined for the ligand 3-(3'-methyl phenylazo) lawsone. The copper complexes of these derivatives were found to possess 1:2 metal stoichiometry and square planar geometries with intermolecular stackings, resulting in antiferromagnetic exchange interactions. The in vitro activity of all the synthesized compounds was examined against human breast cancer cell-line, MCF-7, which revealed enhanced activities for the metal complexes, the highest activity being observed for the copper compound of 3-(3'-methyl phenylazo) lawsone.

Antioxidant and Prooxidant Effects of Metal Dafonates on the NADPH-Dependent Lipid Peroxidation in the Murine Hepatic Microsomal System.

Dafone inhibits the lipid peroxidation significantly in a concentration dependent manner. The inhibition was found to be an uncompetitive type with the inhibition constant (Ki) of 62.5muM On the other hand complexation with metal ions results in a significant reversal from antioxidant to pro-oxidant properties for the resulting complexes which are cationic and with associated halometallate anions. The nature of the potentiation in case of the ferric compound was of competitive type with activation constant (Ka) having the value 32.5muM. The neutral copper-dafonate complex, however, inhibits lipid peroxidation with increase in concentration.