Management of the use of public health pesticides in the face of the increasing burden of vector-borne diseases in the Eastern Mediterranean region.

The Eastern Mediterranean Region of the World Health Organization is facing an increasing burden of vector-borne diseases. Progress in controlling these diseases is compromised by the limited number of vector control interventions, most of which rely on the use of pesticides. Seventeen countries of the Region participated in a global survey that aimed to map and document registration and management practices for public health pesticides. This paper aims to draw the attention of policy- and decision-makers to the challenges the Region is facing in managing public health pesticides properly to control disease vectors and, based on the outcome of the survey, recommends a set of actions to guide national policy and to strengthen national capacity for the sound management and judicious use of public health pesticides.

Folic acid conjugated PAMAM-modified mesoporous silica-coated superparamagnetic iron oxide nanoparticles for potential cancer therapy.

In this study, novel folate-receptor-targeted polyamidoamine (PAMAM) dendrimer functional mesoporous silica-coated magnetic nanoparticles were prepared for drug delivery agents for photodynamic therapy applications. The surface of the magnetic nanoparticles was coated with mesoporous silica (M-MSN). The M-MSN nanoparticles were functionalized with siloxane-cored PAMAM dendrons (generation 1 to 3). The surface of the M-MSN-PAMAM nanocarriers was targeted with folic acid. Indocyanine green (ICG) a near-infrared dye was loaded in the M-MSN-PAMAM nanocarriers and the photodynamic therapy efficiency of the drug-loaded nanocarriers was evaluated on MCF-7 cells. MCF-7 cells were subjected to tissue culture E-Plate that was used to generate dynamic real-time data by measuring electrical impedance across interdigitated microelectrodes on the bottom of the plate. Light source (LEDs) was designed as a system that fit 96 well-plate and cells were irradiated at 785 nm for 20 min. Also, these results were confirmed by WST-1 assay in dark and light conditions for MCF-7 cells. The results showed that in vitro application of ICG loaded M-MSN-PAMAM-FA causes apoptosis in the MCF-7 cell line.

Comparative efficacy and safety of two different molecular weight (MW) hyaluronans F60027 and Hylan G-F20 in symptomatic osteoarthritis of the knee (KOA). Results of a non inferiority, prospective, randomized, controlled trial.

OBJECTIVES: To compare the efficacy and safety of a 'medium' molecular weight (MW) hyaluronan product (F60027, Structovial) with a 'high' MW (Hylan G-F20, Synvisc). METHODS: Prospective, randomised, multicentre, double-blind, active controlled, parallel-group study with a non-inferiority design. Patients with symptomatic KOA, global pain ≥ 40 mm (VAS, 0-100), Lequesne index (LFI, 0-24) score >7 and radiological Kellgren-Lawrence grade 2/3 were centrally randomised to receive F60027 or Hylan G-F20, administered via three weekly injections, with regular follow-up evaluations up to week 24 (W24). The primary outcome was LFI score change over 24 weeks. Secondary outcomes comprised pain VAS, quality of life, patient's and physician's global assessments, rescue medication consumption and OMERACT-OARSI responders rate. RESULTS: 276 patients were analysed in the full analysis dataset (FAS), 236 in the Per Protocol dataset (PP). In the main efficacy analysis (PP), the difference of the LFI score change over 24 weeks between F60027 (-4.67 (0.27)) and Hylan G-F20 (-4.54 (0.28)) was 0.132 [95%CI: -0.598, 0.861] which met the predefined non-inferiority margin. Analyses of secondary efficacy criteria showed clinically relevant improvements of all outcomes at W24 for each treatment on both PP/FAS populations. Changes of LFI score between baseline and W24 were -5.73 in the F60027 and -5.57 in the Hylan G-F20 group (PP dataset). Few local reactions were reported: 3.6% of patients in each group. CONCLUSIONS: F60027 and Hylan G-F20 were equally effective in reducing functional impairment and relieving pain in KOA patients, and well-tolerated.

Implementation of integrated vector management for disease vector control in the Eastern Mediterranean: where are we and where are we going?

Integrated vector management (IVM) is an acknowledged strategy of choice for the prevention and control of vector-borne diseases. The paper describes and documents the progress countries of the World Health Organization (WHO) Eastern Mediterranean Region have made in endorsing and translating the strategy into action at the national level. These include increased political commitment; strengthened intersectoral coordination and partnership; strengthened capacity in entomology and vector control; and scaling up of vector control interventions through universal access. These efforts, however, are compromised by inappropriate institutional arrangements in some countries; weak national capacities to address management of pesticides; , development and spread of vector resistance to insecticides, including to pyrethroids; and the expansion of emerging and re-emerging vector-borne diseases. With WHO leadership and support from partners, countries continue to address these challenges head-on.

Efficacy of two formulations of the bioinsecticide spinosad against Culex quinquefasciatus in India.

Spinosad 12% suspension concentrate (SC) and 0.5% granular (G) formulations were tested against Culex quinquefasciatus immatures at 3 dosages--50, 100, and 150 mg active ingredient (AI)/m2--in cesspits, street drains, and disused wells in comparison with temephos 1% G at 1 part per million. The 2 formulations reduced the density of pupae of Cx. quinquefasciatus by 80-100% for 7-14 days in cesspits, 7-18 days in drains, and 33-69 days in disused wells at the 3 dosages tested. The 12% SC and 0.5% G formulations were equally effective in suppressing the larval and pupal populations of Cx. quinquefasciatus in all the habitats treated. At 100 mg AI/m2 in drains and cesspits, the efficacy of spinosad 0.5% G was greater than that of temephos (1% G) and that of spinosad 12% SC was comparable to that of temephos (1% G) applied to the 2 habitats. In disused wells, both the formulations lasted longer than temephos. Based on the small-scale trial, the rate of 150 mg AI/m2 of spinosad was selected for field application to cesspits and drains and 50 mg AI/m2 for application to disused wells. The efficacy observed in medium-scale trials was in agreement with that of small-scale trials. The trial showed that the 2 formulations of spinosad can be used for larval control of Cx. quinquefasciatus, at 50 mg AI/m2, applied at weekly intervals to cesspits and street drains and at monthly intervals to disused wells. At the higher dose of 150 mg AI/m2, the 2 formulations were effective in suppressing the pupal population for 2 wk in cesspits and street drains and for 2 months in disused wells.

Efficacy of novaluron against Culex quinquefasciatus in small- and medium-scale trials, India.

Novaluron 10% emulsifiable concentrate (EC), an insect growth regulator (IGR), was tested against Culex quinquefasciatus immatures at 1, 5, and 10 mg active ingredient (AI)/m2 applied to cesspits, drains, and abandoned wells. The IGR produced 80-100% inhibition of adult emergence (IE) for > 1 week (10-14 days) in cesspits, 1-2 weeks in street drains, and 5-10 weeks in abandoned wells at the 3 application rates. The efficacy increased with the increasing dose in street drains and abandoned wells. The residual activity of the IGR was longer in abandoned wells compared to drains and cesspits. Based on the small-scale trial, doses of 1, 5, and 10 mg AI/m2 were used in the medium-scale trial for cesspits, abandoned wells, and street drains, respectively. The efficacy observed in medium-scale trial was similar to that in the small-scale trial. The results indicate that novaluron 10% EC can be used for larval control against Cx. quinquefisciatus at the application rate of 1 mg AI/m2 at 10-day intervals in cesspits, at 5 mg AI/m2 at 2-month intervals in abandoned wells, and at 10 mg AI/m2 applied at fortnightly intervals to drains. Even at the lowest rate of 1 mg AI/m2, the IGR prevented adult emergence for at least a week in cesspits and street drains and for a month in abandoned wells. Novaluron 10% EC could be one of the options for larval control operations in integrated vector management.

Field evaluation of an insect growth regulator, pyriproxyfen 0.5% GR against Culex quinquefasciatus, the vector of Bancroftian filariasis in Pondicherry, India.

Pyriproxyfen, 0.5% granular formulation (GR), an insect growth regulator (IGR) was tested against Culex quinquefasciatus larvae and pupae in disused wells, cesspits and drains at the dosages of 0.1, 0.25, and 0.5kg(ai)/ha to determine the most appropriate field dosage. The IGR was found to be effective against C. quinquefasciatus larvae and pupae in all the larval habitats tested. In drains with slow moving water, application of pyriproxyfen 0.5% GR at 0.5kg(ai)/ha resulted in >80% emergence inhibition (EI) of adults for 4 weeks. At 0.1 and 0.25kg(ai)/ha, the EI was always less than 80%. In stagnant drains, the IGR yielded >80% EI for 1-week period at 0.1kg(ai)/ha. At 0.25 and 0.5kg(ai)/ha, the efficacy was 5-10 times higher. In cesspits, the EI was >80% for 6 weeks when pyriproxyfen 0.5% GR was applied at 0.1kg(ai)/ha, for 11 weeks at 0.25kg(ai)/ha and 9 weeks at 0.5kg(ai)/ha. In disused wells treated at the dosage 0.1kg(ai)/ha, there was >80% EI for 15 weeks and at 0.25 and 0.5kg(ai)/ha, the effective duration was about 1.6-1.8 times longer (24-28 weeks). Considering the quantum of IGR required and the cost and also for safety reasons, the low dosage 0.1kg(ai)/ha is recommended as the field dosage to be applied at weekly interval in stagnant drains, 6 weeks interval in cesspits and 15 weeks interval in disused wells. Since pyriproxyfen 0.5% GR has a relatively longer residual effect than the other IGRs the operational cost could be minimized. Pyriproxyfen 0.5% GR could be one of the choices in the chemical control strategy in Integrated Vector Control Programmes.

Glutathione S-transferases in human and rodent skin: multiple forms and species-specific expression.

The glutathione S-transferases (GST) are a family of widely distributed multifunctional detoxification enzymes that catalyze the reaction between reduced glutathione and a variety of electrophiles. Of interest is the fact that several extracutaneous tissues exhibit a distinct spectrum of isozymes that are expressed in a highly controlled fashion. Despite the fact that the skin is continuously exposed to numerous injurious agents, little is known about the expression of GST isozymes and their role in metabolism of physiologic and xenobiotic substrates in cutaneous tissue. Using specific polyclonal antibodies to the Alpha, Mu, and Pi classes of GST, we identified their expression in rat, mouse, and human skin cytosol. In each species, GST isozymes expressed activities towards 1-chloro-2,4-dinitrobenzene, benzo(a)pyrene 4,5-oxide, styrene 7,8-oxide, leukotriene A4, and ethacrynic acid, but not towards bromosulfophthalein and cumene hydroperoxide. Western blot analysis indicated the predominant expression of Pi isozyme in all three species. Alpha class of isozyme(s) was present only in human skin, whereas Mu class of isozyme(s) was detected only in rat and mouse skin. Similarly, in normal and transformed cultured human keratinocytes Pi was the predominant isozyme. In situ localization studies using immunohistochemical techniques confirmed the observations of Western blotting. In mouse skin, Pi and Mu isozyme(s) were found to be predominantly localized in sebaceous glands, whereas no reactivity was observed with the Alpha class of isozymes. Our data show that multiple forms of GST exist in rodent and human skin and that GST Pi is the predominant isozyme in each species. Furthermore, cutaneous GST can metabolize both endogenous substrates and foreign compounds.

Follicular basal cell hyperplasia overlying dermatofibroma.

Follicular basal cell hyperplasia (FBCH) overlying dermatofibroma represents aborted or impeded pilar differentiation. Historically, this hyperplasia has been misinterpreted as basal cell carcinoma. In a large series of dermatofibroma (258 cases), those that contained primitive or malformed follicular structures over the lesion (59 cases) were compared with those without such elements (199 cases). Statistical analysis of various clinicopathologic features showed that FBCH was significantly associated with younger age, trunk location, hypercellular dermatofibroma, loss of a Grenz zone, clear cell hyperplasia, and seborrheic keratosis-like change. There was an inverse correlation between epidermal atrophy, lichen simplex chronicus-like change, and lower extremity location with FBCH. Histologic features favoring a diagnosis of FBCH over basal cell carcinoma are the focal nature and superficial location of the lesion, lack of cytologic atypia and mitoses, recognizable components of hair follicle differentiation, focal condensation of mesenchymal cells around basal cell proliferation, and the association of epidermal hyperplasia. Our findings suggest that FBCH, clear cell hyperplasia, and seborrheic keratosis-like change all represent an expression of follicular differentiation overlying dermatofibroma.

Protective effect of all trans retinoic acid against tumor promotion and progression in low- and high-risk protocols of mouse skin chemical carcinogenesis.

In this study, we assessed the protective effects of all trans retinoic acid (RA) against skin tumor promotion and progression in three different protocols of mouse skin multistage carcinogenesis. Under these protocols, where papillomas on the skin of SENCAR mice were induced for their low- and high-probability of conversion to malignant carcinomas, pre-application of RA (10 mu g/mouse/application) to that of tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA) or mezerein (MEZ) in 7,12-dimethylbenz(a)anthracene (DMBA)-initiated mouse skin resulted in a highly significant protection against skin tumor promotion. In terms of tumor incidence, multiplicity and volume/mouse, at the termination of the experiment at 20 weeks, RA showed 35-80%, 67-83% and 70-98% protection, respectively. While the effect of RA was profound in all the protocols, maximum affectivity was evident in high-risk papilloma induction protocol where DMBA was used as tumor initiator and one week later TPA was applied once a week for five weeks. In tumor progression studies, at 20 weeks of standard low- and high-risk protocols, when papilloma yield is stabilized, animals which did not receive RA in different protocols were divided into two groups and topically treated twice weekly either with acetone or RA (10 mu g). These treatments were continued for an additional 29 weeks. During these treatments, all suspected carcinoma formation was recorded and carcinomas were verified histologically at the termination of the experiment. In each case, RA showed remarkable protective effects against percentage of mice with carcinomas (35-45% protection), number of carcinomas per mouse (50-63% protection) and the rate of malignant conversion (50-63% protection). The results of the present study clearly demonstrate that irrespective of the risk for skin carcinogenesis, RA is capable of affording protection against the induction of nonmalignant lesions and their subsequent conversion to malignancy.

There are some benefits for eradicating Helicobacter pylori in patients with non-ulcer dyspepsia.

BACKGROUND: The relationship between Helicobacter pylori infection and non-ulcer dyspepsia is not established. AIM: To determine whether eradication of H. pylori might be of benefit in non-ulcer dyspepsia patients. METHODS: We randomly assigned 129 H. pylori infected patients with severe epigastric pain, without gastro-oesophageal reflux symptoms, to receive twice daily treatment with 300 mg of ranitidine, 1000 mg of amoxicillin, and 500 mg of clarithromycin for 7 days and 124 such patients to receive identical-appearing placebos. RESULTS: Treatment was successful (decrease of symptoms at 12 months) in 62% of patients in the active-treatment group and in 60% of the placebo group (N.S.). At 12 months, the rate of eradication of H. pylori was 69% in the active-treatment group and 18% in the placebo group (P < 0.001). Complete relief of symptoms occurred significantly more frequently in patients on the active treatment (43%) than in placebo-treated patients (31%, P=0.048). Within the active-treatment group, therapeutic success was significantly more frequent in the non-infected patients (84% vs. 64%, P=0.04). CONCLUSIONS: Although eradicating H. pylori is not likely to relieve symptoms in the majority of patients with non-ulcer dyspepsia, a small proportion of H. pylori-infected patients may benefit from eradication treatment.

Neutrophilic eccrine hidradenitis simulating orbital cellulitis.

Orbital swelling in patients with cancer can reflect neoplastic or infectious processes. Accurate diagnosis can be especially difficult in the face of associated fever and neutropenia. We treated a 30-year-old man undergoing induction chemotherapy for acute myelogenous leukemia, who had fever of unknown origin and periorbital swelling suggestive of orbital cellulitis. However, the periorbital findings were more compatible with passive swelling and hemorrhage. A skin biopsy specimen demonstrated isolated neutrophilic inflammation and necrosis of the eccrine glands. Cultures of the tissue for bacteria and fungi were negative. Pertinent literature regarding eccrine-gland inflammatory disease was reviewed. This unusual entity, termed neutrophilic eccrine hidradenitis, is most common in patients undergoing induction chemotherapy. Cases with infectious causes and cases in neutropenic patients have also been reported. No other patients, to our knowledge, with periocular involvement by neutrophilic eccrine hidradenitis have been described. Neutrophilic eccrine hidradenitis should be added to the differential diagnosis of cases of periocular hemorrhage and swelling in patients with cancer who receive chemotherapy.

Necrolytic acral erythema associated with hepatitis C: effective treatment with interferon alfa and zinc.

BACKGROUND: Necrolytic acral erythema is a recently described necrolytic erythema that is unique in its exclusive acral location and strong association with hepatitis C. OBSERVATION: We report the first case of necrolytic acral erythema in the United States. The patient is a 43-year-old black woman who presented with a 4-year history of tender, flaccid blisters localized to the dorsal aspect of her feet. Serum zinc and glucagon levels were normal. Serum antibodies were positive for hepatitis C, and a liver biopsy specimen showed chronic hepatitis. She was successfully treated with interferon alfa-2b and zinc. We review all previously reported cases. CONCLUSIONS: Necrolytic acral erythema is a distinct entity. In a review of the literature, most patients were between 35 and 55 years of age, although 1 patient was 12 years old. Five of 8 patients were female. Four of 7 patients described previously were treated with variable success using oral zinc sulfate and amino acids, whereas 2 were successfully treated with interferon alfa. All patients were infected with hepatitis C. Necrolytic acral erythema appears to be a skin disorder linked to infection with hepatitis C virus that responds to treatment with interferon alfa and oral zinc.

Knowledge and practice of residents about malaria in southeast Iran (1994).

A survey was undertaken between November 1994 and January 1995 to assess the knowledge and practice with respect to malaria of 1946 randomly selected households in endemic urban and rural areas of Hormozgan, Kerman and Sistan and Baluchistan Provinces, southeast Iran. Knowledge of inhabitants was relatively poor in the study area despite activities to control the disease there for more than 35 years. Mean scores of the knowledge of the residents of the villages having access to primary health care (PHC) services was significantly lower than that under the services of the mobile teams which may reflect the insignificant attention which has been devoted to health education by PHC workers with respect to malaria and malaria control. An educational campaign directed at increasing the knowledge should result in greater acceptance of residents of personal protection methods and vector control and drug treatment programmes.

Apoptosis during photodynamic therapy-induced ablation of RIF-1 tumors in C3H mice: electron microscopic, histopathologic and biochemical evidence.

Very little is known about the applicability of the metabolic and biochemical events observed in cell culture systems to in vivo tumor shrinkage following photodynamic therapy (PDT). The purpose of this study was to assess whether PDT induces apoptosis during tumor ablation in vivo. We treated radiation-induced fibrosarcoma (RIF-1) tumors grown in C3H/HeN mice with PDT employing three photosensitizers, Photofrin-II, chloroaluminum phthalocyanine tetrasulfonate, or Pc IV (a promising phthalocyanine developed in this laboratory). Each photosensitizer was injected intraperitoneally and 24 h later the tumors were irradiated with an appropriate wavelength of red light using an argon-pumped dye laser. During the course of tumor shrinkage, the tumors were removed at 1, 2, 4 and 10 h post-PDT for DNA fragmentation, histopathologic, and electron microscopic studies. Markers of apoptosis, viz. the ladder of nucleosome-size DNA fragments, increased apoptotic bodies, and condensation of chromatin material around the periphery of the nucleus, were evident in tumor tissue even 1 h post-PDT; the extent of these changes increased during the later stages of tumor ablation. No changes were observed in tumors given photosensitizer alone or irradiation alone. Our data suggest that the damage produced by in vivo PDT may activate endonucleolysis and chromatin condensation, and that apoptosis is an early event in tumor shrinkage following PDT.

Apoptosis is an early event during phthalocyanine photodynamic therapy-induced ablation of chemically induced squamous papillomas in mouse skin.

Photodynamic therapy (PDT) is a promising new modality to treat malignant neoplasms including superficial skin cancers. In our search for an ideal photosensitizer for PDT, Pc 4, a silicon phthalocyanine, has shown promising results both in in vitro assays and in implanted tumors. In this study we assessed the efficacy of Pc 4 PDT in the ablation of murine skin tumors; and the evidence for apoptosis during tumor ablation was also obtained. The Pc 4 was administered through tail vein injection to SENCAR mice bearing chemically induced squamous papillomas, and 24 h later the lesions were illuminated with an argon ion-pumped dye laser tuned at 675 nm for a total light dose of 135 J/cm2. Within 72-96 h, almost complete tumor shrinkage occurred; no tumor regrowth was observed up to 90 days post-PDT. As evident by nucleosome-size DNA fragmentation, appearance of apoptotic bodies in hematoxylin and eosin staining and direct immunoperoxidase detection of digoxigenin-labeled genomic DNA in sections, apoptosis was clearly evident 6 h post-PDT at which time tumor shrinkage was less than 30%. The apoptotic bodies, as evident by the condensation of chromatin material around the periphery of the nucleus and increased vacuolization of the cytoplasm, were also observed in electron microscopic studies of the tumor tissues following Pc 4 PDT. The extent of apoptosis was greater at 15 h than at 6 and 10 h post-PDT. Taken together, our results clearly show that Pc 4 may be an effective photosensitizer for PDT of nonmelanoma skin cancer, and that apoptosis is an early event during this process.

[Acid suppression therapy is not required after one-week anti-Helicobacter pylori triple therapy for duodenal ulcer healing]. / La poursuite du traitement antisécrétoire après trithérapie d'éradication de Helicobacter pylori n'est pas nécessaire pour obtenir la cicatrisation des ulcères duodénaux.

AIM: To compare healing of Helicobacter pylori-related non complicated duodenal ulcer after one-week eradication triple therapy alone and after triple therapy with further 3-weeks antisecretory treatment with ranitidine. METHODS: Three hundred and forty three patients with symptomatic H. pylori positive duodenal ulcer were included in this randomized double-blind placebo controlled study. H. pylori infection was established by rapid urease test and histopathology of antral biopsies. All patients were treated for one week with ranitidine 300 mg b.i.d., amoxicillin 1 g b.i.d., clarithromycin 500 mg b.i.d., and then randomly treated for the following 3 weeks either with ranitidine 300 mg once daily (triple therapy + ranitidine, n =180) or placebo (triple therapy alone, n =163). Ulcer healing was assessed by endoscopy 4 weeks after inclusion. H. pylori eradication was established by (13) C-urea breath testing 5 weeks after the end of triple therapy. RESULTS: In intention to treat, duodenal ulcer healed at 4 weeks in 86 % of patients treated with triple therapy + ranitidine and in 83 % of patients treated with triple therapy alone (equivalence: 90 % CI [-3. 8 %; 9.2 %]). The H. pylori eradication rates were 67 % and 69 % respectively. Ulcer healed in 88 % of patients in whom H. pylori eradication was achieved and in 77 % of patients in whom eradication failed. CONCLUSION: These results demonstrate that one-week triple therapy alone is highly effective in healing non complicated H. pylori associated duodenal ulcer without additional antisecretory treatment.

The distribution and larval habitat characteristics of Iranian Culicinae.

The distribution of the Iranian Culicinae is updated and reported by province. Larval habitat characteristics of each species, based on the information gathered throughout its range in Iran and at different times during the breeding season, are also presented.

Malaria control in Iran--present and future.

The malaria eradication campaign in Iran, which started in 1958, has not been able to achieve its final goals. The technical, administrative, socio-economic and financial obstacles involved in this unfinished task are mentioned and the present status of malaria in the country is discussed. It is urged that eradication policy, presently used, be substituted by malaria control program, as defined by The World Health Organization. This would serve as a prerequisite for eventual eradication of malaria, from the country, in the future. Within such agreement, the improvement of basic health services and search for better technical means of controlling the transmission of the infection are emphasized as vital to achieve this goal. Intensive training of experienced staff, in Iran, for stimulation and promotion of relevant research and training activities in malaria control is highly recommended.

Occurrence of Anopheles culicifacies species A in Iran.

Polytene chromosome preparations of the ovarian nurse cells of Anopheles culicifacies females collected in 6 different parts of Baluchistan, Iran, during September-October 1987 and May-June 1988 revealed the existence of species A in this country. The chromosome arms are homosequential with those of species A of India. This report confirms the distribution of species A in Iran.