Evaluation of safety, feasibility and efficacy of intra-ovarian transplantation of autologous adipose derived mesenchymal stromal cells in idiopathic premature ovarian failure patients: non-randomized clinical trial, phase I, first in human.

BACKGROUND: Premature ovarian failure (POF) is characterized by the loss of ovarian activity before the age of 40 years. Stem cell therapy has the capability to create a regenerative microenvironment and is a proposed treatment for POF-related infertility due to the presence of renewal folliculogenesis and germ cells in the adult ovaries. In this study, we assessed the safety, feasibility, efficacy and dose adjustment of autologous adipose-derived stromal cells (ADSCs) and their ability to improve ovarian function in POF patients. METHODS: This study was a non-randomized clinical trial, phase I. Nine women with a definitive diagnosis of POF were divided into three groups (n = 3 per group) that received either 5 × 106, 10 × 106, or 15 × 106 autologous ADSCs suspension transplanted in the one ovary. Participants were followed-up at 24 h after the transplantation, and at 1 and 2 weeks, and 1, 2, 3, 6, and 12 months after the transplantation. The primary objective was to evaluate the safety of ADSCs transplantation. Secondary objectives included the effects of ADSCs transplantation on the resumption of menstruation, hormones level (Follicle-stimulating hormone (FSH) and anti-Müllerian hormone), ovarian function (Antral follicle count and ovary volume by ultrasonography evaluation) as well as dose escalation. RESULTS: Participants had not shown any early-onset possible side effects and secondary complications during follow-up. The menstruation resumption was observed in four patients which established for several months. In the 15 × 106 group, two POF patients had a return of menstruation second months after the intervention. Two other POF patients in 5 × 106 and 10 × 106 cell groups reported menstruation resumption at 1 month after the intervention. We observed decreased serum FSH levels of less than 25 IU/l in four patients. In two patients in 5 × 106 and 10 × 106 cell groups, serum FSH showed an inconsistent decline during a 1 year follow up after ADSCs transplantation. The ovarian volume, AMH, and AFC were variable during the follow-up and no significant differences between cell groups (p > 0.05). CONCLUSIONS: We showed the intra-ovarian embedding of ADSCs is safe and feasible and is associated with an inconsistent decline in serum FSH. This should be further investigated with a large RCT. TRIAL REGISTRATION: NCT02603744 , Registered 13 November 2015 - Retrospectively registered, http://www.Clinicaltrials.gov.

Spatial distribution and molecular identification of leishmania species from endemic foci of South-eastern iran.

BACKGROUND: Cutaneous leishmaniasis constitutes a major public health problem in many parts of the world including Iran. The primary objective of this study was to identify Leishmania species in endemic districts of Kerman Province, south-eastern Iran. METHODS: This study was conducted by random sampling as cross- sectional descriptive between 2008 and 2010. Overall, 203 skin scraping smears were taken from the patients. Nested -PCR was performed to amplify variable minicircle fragments of Leishmania kDNA. RESULTS: Bam was the most infected district (71.1%), followed by Kerman (14.7%), Jiroft (5.4%), Baft (2.7%), Sirjan (1.6%), Shahr-e Babak (1.5%) and others (3.0%). L. tropica was the most common species identified (194 cases, 95.6%), while L. major was found in only 9 cases (4.4%). Of 203 identified patients, all species in Bam (l07 cases), Kerman (32 cases), Jiroft (l6 cases) and Shahr-e- Babak (l1 cases) were detected as L. tropica, whereas infected subjects in Baft and Sirjan showed L. tropica or L. major. Characterization of Leishmania species resulted in generation of 750 bp and 560 bp fragments, corresponding to those of L. tropica and L. major, respectively. CONCLUSION: L. tropica is the main species (95.6%) caused ACL in endemic areas of Kerman Province; however L. major is present in low level (4.4%).

Residual Effects of Deltamethrin WG 25% as a New Formulation on Different Surfaces against Anopheles stephensi, in Southeastern Iran.

BACKGROUND: Indoor residual spraying (IRS) is functioned as national interventions against malaria in southeastern foci of Iran and deltamethrin WP one of the insecticides have been used since past decade. In this study, the residual activity of the wettable granule (WG) was studied on different surfaces in hut scale trial against Anopheles stephensi in Iranshahr District, southeastern Iran. METHODS: Three dosages of 25, 40 and 50 mg a.i./m(2) of deltamethrin WG 25% formulation were applied on plaster, cement, mud, and wooden surfaces using Hudson(®) X-pert compression sprayer having 10 litters capacity. RESULTS: The residual effects of deltamethrin WG 25% on different surfaces was assessed based on reduction of mortality An. stepehnsi from 100% to about 70%. At 25, 40 and 50 mg a.i./m(2) the WG formulation of deltamethrin had a bioefficacy for about 2, 3 and 4 months respectively. CONCLUSION: There was an expectable fluctuation in mortality of An. stephensi at different sprayed surfaces as well as dosages. The proposed 50 mg/m2 WG is the longest activity for up to 4 months which needs to be applied for two spraying cycles per year at the climatically condition of southwestern Iran.

Comparative performance of imagicides on Anopheles stephensi, main malaria vector in a malarious area, southern Iran.

BACKGROUND & OBJECTIVES: Jiroft district has subtropical climate and prone to seasonal malaria transmission with annual parasite index (API) 4.2 per 1000 in 2006. Anopheles stephensi Liston is a dominant malaria vector. The monitoring of insecticide susceptibility and irritability was conducted using discriminative dose as described by WHO. METHODS: The IV instar larvae were collected from different larval breeding places and transported to the temporary insectary, fed with Bemax and then 2-3 days-old emerged and sugar-fed adults were used for susceptibility and irritability tests employing WHO methods and kits to organochlorine (OC) and pyrethroid (PY) insecticides. RESULTS: Mortality rates of field strain of An. stephensi were 91.3 +/- 0.14 and 90 +/- 0.47% to DDT and dieldrin, respectively at one hour exposure time but was susceptible to all pyrethroids tested. The average number of take-offs per min per adult was 2.09 +/- 0.13 for DDT, 0.581 +/- 0.05 for dieldrin, 1.85 +/- 0.08 for permethrin, 1.87 +/- 0.21 for lambda-cyhalothrin, 1.53 +/- 0.13 for cyfluthrin, and 1.23 +/- 0.1 for deltamethrin. INTERPRETATION & CONCLUSION: Currently, deltamethrin is being used for indoor residual spraying against malaria vectors in the endemic areas of Iran. The findings revealed that the main malaria species is susceptible to all pyrethroids including deltamethrin, permethrin, cyfluthrin and lambda-cyhalothrin but was tolerant to DDT and dieldrin. This report and the finding are coincided with results of previous studies carried out during 1957-61 in the same area. Irritability tests to OC and PY insecticides revealed the moderate level of irritability to DDT compared to pyrethroids and dieldrin. Monitoring for possible cross-resistance between OC and PY insecticides should come into consideration for malaria control programme.

Role of natural killer cell subsets in cardiac allograft rejection.

To achieve donor-specific immune tolerance to allogeneic organ transplants, it is imperative to understand the cell types involved in acute allograft rejection. In wild-type mice, CD4(+) T cells are necessary and sufficient for acute rejection of cardiac allografts. However, when T-cell responses are suboptimal, such as in mice treated with costimulation-targeting agents or in CD28-deficient mice, and perhaps in transplanted patients taking immunosuppressive drugs, the participation of other lymphocytes such as CD8(+) T cells and NK1.1(+) cells becomes apparent. We found that host NK but not NKT cells were required for cardiac rejection. Ly49G2(+) NK cells suppressed rejection, whereas a subset of NK cells lacking inhibitory Ly49 receptors for donor MHC class I molecules was sufficient to promote rejection. Notably, rejection was independent of the activating receptors Ly49D and NKG2D. Finally, our experiments supported a mechanism by which NK cells promote expansion and effector function of alloreactive T cells. Thus, therapies aimed at specific subsets of NK cells may facilitate transplantation tolerance in settings of impaired T-cell function.

Monitoring of insecticides resistance in main malaria vectors in a malarious area of Kahnooj district, Kerman province, southeastern Iran.

BACKGROUND AND OBJECTIVES: Kahnooj district in south of Iran is an endemic area for malaria where Anopheles stephensi (Liston) is a main malaria vector and An. dthali (Patton) a secondary vector. According to the national strategy plan on monitoring of insecticides resistance, this study was performed on susceptibility and irritability levels of An. stephensi and An. dthali to different insecticides in the district. METHODS: The susceptibility and irritability levels of field strains of An. stephensi and An. dthali at the adult and larval stages to discriminative dose of different imagicides was determined as recommended by WHO. RESULTS: Using discriminative dose and WHO criteria it was found that An. stephensi is resistant to DDT and dieldrin with 36.1 +/- 2.3 and 62.2 +/- 1.95 mortality rates, respectively; but susceptible to other insecticides. An. dthali was found to susceptible to all tested insecticides. The larvae of An. stephensi, exhibited 100% mortality for temephos and malathion, but 44 +/- 4.32 for discriminative dose of fenitrothion. The results of irritability level for DDT and pyrethroids showed that permethrin had the most irritancy effect on An. stephensi and An. dthali. DDT and deltamethrin showed the least irritancy effect against An. stephensi with 0.42 +/- 0.08 and 0.77 +/- 0.12 take-offs/min/adult, respectively, however, lambdacyhalothrin had the least irritancy effect against An. dthali with 0.096 +/- 0.02 take-offs/min/ adult. The mean number of take-offs/min/adult with permethrin showed significant difference to DDT, lambdacyhalothrin, cyfluthrin and deltamethrin. INTERPRETATION AND CONCLUSION: Pyrethroid insecticides are being used as indoor residual sprays in Iran. Based on our results, the main malaria vectors in the region are still susceptible to pyrethroid insecticides. Therefore, we propose the use of pyrethroids with low irritancy effect in rotation with carbamate insecticides in two interval seasonal peaks of malaria transmission. Biological control including larvivorous fishes, using of local made Bacillus thuringiensis and larvicides such as chlorpyrifos-methyl are the main larval control in the region. Result on larval test exhibited the susceptibility of main vectors to some larvicides, although the 100% mortality was not obtained using fenitrothion and this is postulated the use of this insecticide in agriculture pest control. Monitoring and evaluation of insecticides resistance in malaria vectors in the region could provide an essential clue for judicious use of insecticides.

Peripheral survival of naïve CD8+ T cells.

Maintenance of a sufficient population of naive CD8+ T cells in the peripheral lymphoid compartment is critical for immunocompetence. Peripheral T cell number is a function of T cell generation, survival, and death. Homeostasis, a critical balance between survival and death, must exist to prevent either lymphopenia or lymphocytosis. In the current review, we discuss known requirements for the survival of naive peripheral CD8+ T cells as well as mechanisms of death when survival signals are lost. We also discuss associations between survival and homeostasis-driven proliferation, and highlight the gaps in our knowledge of these critical processes.