Development of polyvinylpyrrolidone/paclitaxel self-assemblies for breast cancer

The goal of this investigation was to develop and demonstrate a polymer/paclitaxel self-assembly (PTX-SA) formulation. Polymer/PTX-SAs were screened based on smaller size of formulation using dynamic light scattering analysis. Additionally, fluorescence microscopy and flow cytometry studies exhibited that polyvinylpyrrolidone (PVP)-based PTX-SAs (PVP/PTX-SAs) had superior cellular internalization capability in MCF7 and MDA-MB-231 breast cancer cells. The optimized PVP/PTX-SAs exhibited less toxicity to human red blood cells indicating a suitable formulation for reducing systemic toxicity. The formation of PVP and PTX self-assemblies was confirmed using fluorescence quenching and transmission electron microscopy which indicated that the PVP/PTX-SAs were spherical in shape with an average size range of 53.81 nm as detected by transmission electron microscopy (TEM). FTIR spectral analysis demonstrates incorporation of polymer and paclitaxel functional groups in PVP/PTX-SAs. Both proliferation (MTS) and clonogenic (colony formation) assays were used to validate superior anticancer activity of PVP/PTX-SAs in breast cancer cells over paclitaxel. Such superior anticancer activity was also demonstrated by downregulation of the expression of pro-survival protein (Bcl-xL), upregulation of apoptosis-associated proteins (Bid, Bax, cleaved caspase 7, and cleaved PARP) and -tubulin stabilization. These results support the hypothesis that PVP/PTX-SAs improved paclitaxel delivery to cancer cells.

Prevalence of plasmid mediated pesticide resistant bacterial assemblages in crop fields.

Three crop fields namely, paddy, sugarcane and tomato exposed to bavistin [Methyl (1H-benzimidazol-2-yl) carbomate], monocrotophos [Dimethyl (E)-1-methyl-2-(methyl-carbamoyl) vinyl phosphate] and kinado plus [(EZ)-2-chloro-3-dimethoxyphosphinoyloxy- X1, X1-diethylbut-2-enamide], respectively were chosen for the present investigation to know the bacterial population and degradation of pesticides. The chemical nature of the soil and water samples from the pesticide contaminated fields was analysed along with counting of the total heterotrophic bacteria (THB), Staphylococci and Enterococcci population. Mean calcium, phosphate and biological oxygen demand were maximum in tomato field water. Field water recorded maximum phophate and silicate content, whereas, sugarcane field water elicited maximum dissolved oxygen content. On the other hand, available phosphate and exchangeable potassium were maximum is sugarcane field soil. Significant variations in the bacterial population were evident between the treatments in sugarcane field soil and tomato field water exposed to monocrotophos and kinado plus, respectively. In addition, significant variations between THB, Staphlyococci and Enterococci population were also evinced in both the sugarcane and tomato fields. The dominant pesticide resistant bacteria, Staphylococcus aureus, Enterococcus faecalis and Pseudomonas aeuroginosa harboured plasmids and the resistant trait observed were found to be plasmid borne.

Reuse of polyethylene waste in road construction.

The cost of construction of flexible pavements depends on thickness of the pavement layers. The thickness of pavement mainly depends on the strength of the subgrade. By suitable improvement to the strength of the subgrade, considerable saving in the scarce resources and economy can be achieved. Because of their lightweight, easy handling, non-breakable and corrosion free nature, polyethylene have surpassed all other materials in utility. But polyethylene waste has been a matter of concern to environmentalists as it is non-biodegradable. In this investigation, an attempt has been made to study the improvement of California Bearing Ratio (CBR) value of soils stabilized with waste polyethylene bags. This alternative material is mixed in different proportions to the gravel and clay to determine the improvement ofCBR value. Use of the waste polyethylene bags observed to have a significant impact on the strength and economy in pavement construction, when these are available locally in large quantities.

Comparative efficacy and safety evaluation of cefaclor vs amoxycillin + clavulanate in children with Acute Otitis Media (AOM).

Acute Otitis Media (AOM) is the most frequent respiratory tract infection of infancy and childhood that is treated with antimicrobial agents. The most common causative pathogens include Streptococcus pneumoniae, Hemophilus influenzae and Moxarella catarrhalis, and therefore antibacterial management should target against these isolates. Cefaclor, a congener of cephalexin monohydrate, is a semisynthetic cephalosporin antibiotic. It is an orally active cephalosporin which has demonstrated activity against a wide range of organisms in vitro. Present study is designed as a multicentric prospective trial to study and compare the efficacy and safety of cefaclor versus amoxicillin + clav in children with acute otitis media. One hundred and sixty seven patients were evaluated for efficacy endpoints in the cefaclor arm comprised of 104 males and 63 females with a mean age of 5.74+/-2.80 years and 185 patients in the amoxy-clav group comprised of 118 males and 67 females with a mean age of 4.93+/-2.92 years. Both cefaclor and amoxy-clav caused a significant improvement in all the signs and symptoms after a 10-day treatment period. However, between-the-group comparisons showed that the reduction in most of the symptoms was significantly more in cefaclor arm as compared to amoxicillin-clav arm. The clinical success (clinical cure + improvement) at the end of therapy was significantly more in cefaclor arm: 98% with cefaclor versus 85% with amoxicillin + clav, p<0.05 Table 3. Failure cases were prescribed other antibiotics according to the culture sensitivity reports, as rescue medication. Bacterial eradication rates were largely consistent with clinical responses. Bacteriological eradication was seen in 95% of patients in cefaclor group and 78% of patients in amoxicillin + clav group. In conclusion, cefaclor is a well tolerated and effective antibacterial option for acute otitis media in children and it is superior to the combination of amoxicillin + clav in efficacy and tolerability in acute AOM. Moreover, its expanded spectrum of activity, ability to achieve adequate concentrations in tissues, suitability for twice-daily dosing, and proven tolerability suggest that it is a good alternative to agents traditionally used in acute otitis media.

DOTS strategy for control of tuberculosis epidemic.

The article reviews the elements of the DOTS strategy to control the tuberculosis epidemic WHO declared TB" a global emergency" in 1993, the impact of which is worsened by the emergence of multi drug-resistant TB (MDR-TB) and the spread of HIV/AIDS. DOTS (directly-observed treatment, short-course) is an intermittent, supervised system of drug-intake by patient, which eliminates drug-default. It has been described by WHO as "the most important public health breakthrough of the decade in terms of lives saved" The 5 major components of DOTS are i) Political will, ii) High-quality microscopy, iii) Uninterrupted supply of short-course chemotherapy drugs, iv) Directly--observed chemotherapy regimen use, v) Systemic monitoring using the TB cure rate. Standardized, intermittent DOTS regimens are classified using three categories of disease. The main advantages of DOTS are (i) Cure rates of upto 95%, (ii) Prevention of MDR--TB emergence, (III) Improvement of longevity of AIDS patients by TB control, (iv) It is "one of the most cost-effective of all health interventions", according to World Bank.

An outbreak of poliomyelitis in Andhra Pradesh (South India).

An outbreak of poliomyelitis that occurred in the year 1992 in Telangana region of Andhra Pradesh, South India was investigated to understand the reasons for persistence of poliomyelitis in the general population and for the outbreak in Andhra Pradesh in particular. The study comprised of a detailed investigation of epidemiological and clinical features, serology and vaccination status and a case control study to calculate vaccine efficacy by matched pair analysis. The outbreak occurred after a relative quiescence of 3 years. The age group of the patients ranged from 2 months to 5 years, 26.5% being infants and 70.2% being children between 1 and 5 years. The outbreak was mainly caused by Type 1 poliovirus. Vaccine efficacy was found to be 70%. Antibody response was not high in cases. Seventy six per cent of the children with poliomyelitis were unvaccinated. Ignorance of the mothers and family interference were the main causes for not vaccinating the children. The study indicates the need to increase the vaccination coverage and inclusion of children upto 5 years in the programme. Absence of vaccination is the major risk factor for the outbreak. The persistence of poliomyelitis in older children, low antibody response and suboptimal vaccine efficacy point out the problem of achieving control with OPV in tropical countries and suggest the need for alternate strategies. Better health education strategies need to be developed.

Factors influencing survival in esophageal atresia.

There is little published literature from the third World countries that described the factors influencing survival of babies with esophageal atresia. We analysed 25 consecutive neonates treated for esophageal atresia. The overall survival rate was 36%. All 4 babies in Waterston Group A, 37.5% in Group B, and 15.4% in Group C survived. All 9 preterm babies died. Only 2 of the 16 babies who had pre-operative chest infection survived. The mean delay in diagnosis was 54 h in outborn babies and 20 h in hospital-born babies. We believe that a survival rate of 40% is easily achieved with minimum infrastructural inputs. Simple methods and practices that would vastly improve operative results have been suggested.

Clinical profile of klebsiella septicemia in neonates.

A detailed clinical study of 51 consecutive cases of neonatal klebsiella septicemia was carried out prospectively over a 20 months period. The incidence was 6.27 per 1000 live births. Majority (85.5%) were either preterms or small for date. Almost fifty percent babies had associated perinatal risk factors. Mean age of onset was 5.7 +/- 2.2 days. General symptoms were the earliest to occur at mean age of 5.7 days followed by respiratory, alimentary, hematological and neurological symptoms at 6.2, 6.3, 6.6 and 7.9 days respectively. About half of the neonates had associated complications; commoner being meningitis (20%), bleeding manifestations and sclerema (17.6% each) and pneumonia (15.7%). Cefatoxime was found to be the drug of choice (86% sensitivity). Nine babies (17.6%) died during the study period at a mean age of 9.1 +/- 3.2 days. Mean duration of hospital stay in rest of neonates was 27.9 +/- 12.1 days. Neurological symptoms were commoner in late onset disease. Bleeding manifestations, sclerema and granulocytopenia were seen exclusively in preterms. Presence of respiratory symptoms, bleeding, sclerema, shock and granulocytopenia were identified as poor prognostic factors in neonatal klebsiella septicemia.

Prognostic score for kerosene oil poisoning.

Ninety five consecutive children with kerosene oil poisoning were studied, the first 70 retrospectively (internal group) and the rest 25, prospectively (external group) over a period of 3 years and 8 months. Based on clinical features and severity of illness in initial 70 cases, a weighted scoring system to determine the outcome was evolved. This included: (i) fever--absent 0, present 1; (ii) severe malnutrition--absent 0, present 1; (iii) respiratory distress--absent 0, present 2, with cyanosis 4; and (iv) neurological symptoms--absent 0, present 2, with convulsions 4. The scores ranged from 0 to 10 in the internal group. Using discriminate function analysis, a score of 4 or more was found to be associated with prolonged hospital stay and complications. The risk of dying increased if the score was equal to or more than 8. The predictive value of the score was 85.7%. For validation, this scoring was applied to the external group as well and 84% of cases could be correctly predicted.

Kerosene oil poisoning--a childhood menace.

This study documents 3-year retrospective analysis of accidental kerosene oil poisoning in 70 children with regard to clinical profile, radiological changes and outcome. About 77% of cases were between 1 and 3 years old. Fifty children (71.4%) developed significant symptoms, with onset soon after to within 10 hours of ingestion. These included breathlessness (55.7%), fever (47.1%), cough (31.4%), restlessness (25.7%) and abdominal distension (15.7%). Chest X-rays were obtained in 65 children. Abnormal radiographs were seen in 45 (69.2%) children with right basal infiltrates being the commonest picture (21.4%). Ingestion of more than one ounce of kerosene oil adversely affected the clinical and radiological profile. Severely malnourished children had extensive radiological changes and poorer clinical outcome. One case developed myocarditis, a complication which has not been reported to the best of our knowledge. Mortality rate was 4.3%. All deaths occurred within 48 hours of admission.

Evaluation of social marketing of oral rehydration therapy.

Attempts, at social marketing of oral rehydration therapy (ORT) through television, in changing the knowledge and practice of mothers with regard to its use was assessed. One hundred and eighty seven consecutive mothers (38 excluded due to non use of ORT) were administered a preplanned questionnaire to assess their socio-economic profile, educational status, concept of diarrhea and correct use of ORT. Fifty nine mothers who watched these programmes on TV regularly formed the study group. These were compared with 90 mothers who had gained such knowledge from non-television sources. The correct application of knowledge of ORT was significantly better in study group compared with control group. The educational status of mothers had a positive impact on motivation to use ORT at home in the study group. Mass media campaigns through "TV spots" is an effective way of improving knowledge of mothers on ORT in a developing country.

Multi drug resistant Salmonella typhi infection: clinical profile and therapy.

Multiple drug resistant Salmonella typhi infection was observed in thirty five recent cases among forty eight children with bacteriologically proven enteric fever. Incidence of complications such as shock, myocarditis, encephalopathy and paralytic ileus was higher among these. A combination of cephalexin and gentamicin was successfully used in the management of these children.