Identification of Two Novel Hydroperoxide Impurities in Fluocinolone Acetonide Topical Solution by Liquid Chromatography Mass Spectrometry.

Fluocinolone acetonide topical is used to treat skin discomforts such as swelling, itching and redness by activating the natural substances in the skin. Several process-related impurities and degradation products are identified and reported. But hydroperoxide impurities in Fluocinolone acetonide topical solution are not reported anywhere. In this study, we identify two potential genotoxic isomeric hydroperoxide impurities in Fluocinolone acetonide topical solution by Liquid Chromatography Mass Spectrometry analysis. A possible mechanism for the formation of these two novel hydroperoxide impurities is based on the neighboring group participation effect of adjacent hydroxyl group (Internal SN2) which results in the loss of fluorine atom and formation of epoxide intermediate followed by the addition of the HOOH group. Since most of the hydroperoxide impurities are genotoxic in nature, one should eliminate these impurities from Active Pharmaceutical Ingredient (API) or protect the formulation product from these oxidative impurities.

Synthesis and biological evaluation of diaryl ether linked DC-81 conjugates as potential antitumor agents.

A series of new diaryl ether linked pyrrolobenzodiazepine (PBD) conjugates (4a-i, 5a-i and 6a-f) was synthesized and evaluated for their anticancer activity against a panel of 11 human cancer cell lines. These conjugates exhibited significant anticancer activity with GI50 values in the range of 0.1-3.88 µM. Some of the potent conjugates (4b, 4h, 5h, 6b, 6c and 6e) were further investigated on cell cycle distribution. FACS analysis showed the accumulation of cells in G0 phase indicating the apoptosis inducing nature of these conjugates. Moreover, compound 6b caused a decrease in the mitochondrial membrane potential, which indicates the apoptotic nature of the compound through mitochondrial mediated pathway. Further conjugates 4b, 4h and 6b induce the activation of caspase and PARP proteins, followed by apoptotic cell death in MCF7 cell line.

Synthesis and biological evaluation of combretastatin-amidobenzothiazole conjugates as potential anticancer agents.

A series of combretastatin-amidobenzothiazole conjugates have been synthesized and evaluated for their anticancer activity. All these compounds exhibited significant anticancer activity and the most potent compound (11a) showed GI(50) values ranging 0.019-11 µM. Biological studies such as cell cycle distribution, effect on tubulin polymerization and effect on ERK signalling pathway have been examined in MCF-7 cell line. FACS analysis revealed that these compounds induced cell cycle arrest at G2/M phase. Compound 11a showed significant effect on tubulin polymerization and affected the ERK signalling pathway that result in the decreased levels of ERK1/2, p-ERK and c-Jun proteins. Docking experiments have shown that the active molecules interact and bind well in the ATP binding pocket of ERK protein.

Synthesis, biological evaluation of 5-carbomethoxymethyl-7-hydroxy-2-pentylchromone, 5-carboethoxymethyl-4',7-dihydroxyflavone and their analogues.

In this letter, we describe the first synthesis of two recently isolated flavones 5-carbomethoxymethyl-7-hydroxy-2-pentylchromone (3a), 5-carboethoxymethyl-4',7-dihydroxyflavone (3b) and their derivatives (3c-t), evaluated for their antimicrobial, antioxidant and anticancer activities. Most of the synthesized compounds exhibited antimicrobial activity against the tested microbial strains and some of these compounds were found to be more potent as compared to the standard drugs like neomycin and luteolin. Interestingly, some of these synthesized compounds also showed moderate antioxidant property.

Do we really know how to respond to an unexpected event during the fitting of an intra-uterine contraceptive device?

OBJECTIVE: To assess and improve knowledge of correct resuscitation procedures if an unexpected event occurs during an intra-uterine device (IUD) fitting. DESIGN: Previous literature on resuscitation in the family planning clinic was reviewed to provide a basis for a questionnaire for doctors and nurses within the service to assess knowledge of correct procedures. Outcome of first questionnaire: Seventeen questionnaires were returned in the first round, of which 12 were from nurses. The results to the first question gave a 70% correct response rate. The response to the second gave a correct response of 41%. Only six out of 17 would give atropine in a vaso-vagal attack. INTERVENTION: The results were discussed at an audit meeting and most staff said that they wanted further training. This was linked with the Leeds Community and Mental Health Trust training for resuscitation. By linking to this training programme it saved time and resources for the family planning service. Outcome of second questionnaire: Twenty-one staff returned questionnaires, of which 12 were nurses. The results to the first question gave an 87% correct response rate. The response to the second showed a correct response of 71%. Fourteen out of the 21 replying would give atropine. CONCLUSION: A service cannot assume that staff know what to do in an emergency if it is rarely encountered. This audit showed that it is possible to raise knowledge standards through a training programme.

Experiences of termination of pregnancy in a stand-alone clinic situation.

This paper describes the authors' experience of conducting termination of pregnancy on conscious patients in community settings. If patients are appropriately selected and prepared, and the procedure conducted in the presence of well-trained and motivated nursing assistance, the method described is successful, safe and acceptable to patients.

Removal of colour and turbidity in pulp and paper mill effluents using polyelectrolytes.

The present study was undertaken for removal of the colour, turbidity and COD from pulp and paper mill effluents using polyelectrolytes for pollution control and its safe disposal. Based on the pH of effluent and nature of colour imparting substance, suitable polyelectrolytes have been selected and used. A novel method of treating the above effluent with 0.2 ml/L of Rishlyte 80 L for the removal of colour, turbidity and COD has been found to be optimal and techno-economically viable when compared with the conventional method of treatment with alum.

Auditing the introduction of a new product to a family planning service.

The audit aimed to develop a questionnaire to monitor how a new method od contraception is offered in service by identifying local demand and assessing levels of awareness of and interest in a new product (Mirena(R)) The audit also aimed to establish those suitable for Mirena and the numbers of Mirena fitted and characteristics of recipients.

PIP: The National Coordinating Unit for Clinical Audit in Family Planning relies on pilot sites throughout the UK to develop informational materials about new products. Described in this paper is an audit conducted in Chesterfield Community Services (North Derbyshire Community Health Trust) in 1996 with the aim of developing a questionnaire for identifying local awareness of and demand for the Mirena IUD. Family planning staff completed questionnaires for 57 new patients or women requesting a change in contraceptive method. Of the 49 women who identified their current method of contraception, 29 were using condoms, 14 were on the pill, and 2 were IUD users. 41 consultations (72%) included a discussion of Mirena; in the remaining 16 cases, the women had decided on a method prior to consultation. 21 women had heard of the Mirena IUD before their visit to the clinic and 18 expressed an interest in it. Only 7 women actually obtained a Mirena IUD; in 1 other case, the device was not available at the clinic. Another 7 women opted for a copper IUD. The mean age of Mirena acceptors (32.9 years) was significantly higher than the mean age of the sample (28.2 years). Of concern is the possibility that women who want Mirena will be directed toward less expensive IUDs in greater supply in UK clinics. It is recommended that a protocol be established for cases in which Mirena is preferred and suitable, but no supply is available.

Introduction of Gynefix as a choice in reproductive health care.

PIP: Marie Stopes International (MSI) provides reproductive health care worldwide through more than 100 projects in over 20 countries. The author reports her experience training MSI staff in Kenya about Gynefix. The several-day course of training was provided at the central Kencom clinic in Nairobi to the two local doctors, nurses from the surrounding clinics, and representatives from Tanzania. The nurses were senior tutors in their own centers who, after training, would train health personnel on Gynefix in their areas. Experience gained through training would also be disseminated to Tanzania, Ethiopia, and Uganda. The technology was first taught using foam models and a pelvic model, then among method acceptors who volunteered to participate in the hands-on training. The trained nurses and doctors were equally competent in and comfortable with providing Gynefix. Reproductive health care services in the UK should follow MSI's example of providing comprehensive reproductive health care services and choices in local communities and outlying facilities.^ieng

Intrauterine contraception. Effective practice and quality of care. A - Z of audit.

PIP: A 1976 review of use of the IUD, which has been available for decades in the UK, included the recommendations that IUD service undergo continued monitoring and that service providers undergo insertion training to become accredited. Today, a training schedule for IUD fitting is in place, but the requirement that a log be kept available for clinical and multiprofessional audit has been dropped. This is unfortunate because a log book is a useful data collection and monitoring tool, especially as it permits monitoring of IUD removal rates. Correct fitting of IUDs as well as correct counseling can minimize removal rates. A chart is, therefore, provided to illustrate the use of monitoring of IUD service provision by listing reasons for removal (pregnancy, infection, discomfort/unacceptable bleeding; dyspareunia, or shock) and relevant standards and changes that can be monitored in each case.^ieng

Autosomal dominant zonular cataract with sutural opacities in a four-generation family.

PURPOSE: We identified and examined four generations of a family with coexisting autosomal dominant zonular cataracts and sutural opacities and sought to determine their genetic basis. METHODS: Twenty-four of the 48 members in the family were examined. Systemic and ocular histories were obtained, and a detailed ophthalmic examination was performed. From each individual, 20 ml of blood was drawn for linkage studies with microsatellite markers in regions to which zonular cataracts had previously been localized (chromosomes 1, 2, and 16). RESULTS: Individuals of the first generation were reportedly asymptomatic. Several members of the second generation had morphologically identical zonular cataracts. Affected members of the third generation showed morphologic heterogeneity, with the zonular opacity varying from a uniform lamella to a segregation of dots. A high degree of consanguinity in the second generation suggested recessive inheritance with a pseudodominant inheritance pattern. However, examination of one member of the asymptomatic first generation disclosed senile cataractous changes superimposed on a faint zonular cataract enclosing sutural opacities and a pulverulent fetal nucleus. The latter findings were reconfirmed to be present in affected members of all generations, suggesting an autosomal dominant mode of inheritance. Initial efforts at linkage analysis excluded the gene locus causing this cataract from the Duffy, haptoglobin, and gamma-crystallin regions. CONCLUSIONS: The cataract in this family is both phenotypically and genetically distinct from previously described and mapped cataracts.

Genetic structure of the Manne Dora, a tribal population of Andhra Pradesh.

The Manne Dora, a small tribe inhabiting the north coastal districts of Andhra Pradesh, South India, have been studied for 24 genetic markers, including blood groups, plasma proteins, and red cell enzymes. A genetic distance analysis was used to test whether this tribe was part of another tribe, the Konda Dora, and to clarify its divergence from other tribal populations of Andhra Pradesh. The dendrogram and principal components analysis reveal clustering of the tribal populations in close agreement with geographic distance. The study indicates that the Manne Dora may have been genetically part of the Konda Dora and separated only recently.

Cervico-thoracic neurenteric cyst: clinicoradiological correlation with embryogenesis.

Two cases of cervico-dorsal neurenteric cysts are presented, one located dorsal and the other ventral to the spinal cord, with associated Klippel-Feil anomaly, meningocele, spinal dysraphism and possibly spinal cord malformation. One patient was operated on as a neonate for a cervico-thoracic meningocele and presented during adolescence with spastic quadriparesis. Imaging revealed spina bifida, a dorsally located neurenteric cyst and a tendency towards split cord malformation. The other child presented with cervico-thoracic kyphoscoliosis and paraparesis. Imaging demonstrated persistence of a cervico-thoracic remnant of the primitive neurenteric canal through the upper thoracic spine.