Evaluation of Laboratory Findings of Patients with Coronavirus Disease 2019 in Kerman, Iran.

Background & Objective: Since December 2019 in Wuhan, China there is a new form of pneumonia and after expansion in other countries, World Health Organization (WHO) called it Coronavirus Disease 2019 (COVID-19). Since the clinical laboratory findings have played an important role in the progression of the disease, this study aimed to evaluate the laboratory findings in COVID-19 patients (before vaccination). Methods: In this case-control study that was conducted from February to August 2020; the laboratory test status in 101 positive COVID-19 patients was evaluated and compared with 101 healthy individuals. Results: The results of our study showed that 21% of patients had low WBC, 24.75% low RBC, 37.62%, low Hb, 18.81% with low HCT, 29.7%, low Plt, 41.58% had High PT, 71.29% high CRP, 17.82% high urea, 11.88% high CR, 15.84% high LDH, 10.89% low sodium, 14.75% low potassium (K). The quantitative examination of blood factors showed that lymph%, mixed%, PLT, HCT, Hb, and RBC were higher in the control group than in the case group. While Neu%, WBC, PTT, CRP, UREA, LDH, K in the patient group were higher than in the control group. Conclusion: According to the results of the study, it can be concluded that in the clinical treatment of COVID-19 patients, much attention should be paid to the laboratory indicators to identify and intervene early in critically ill patients.

Ameliorating age-dependent effects of resveratrol on VPA-induced social impairments and anxiety-like behaviors in a rat model of neurodevelopmental disorder.

Although anxiety disorders, as well as difficulties in social interaction, are documented in children with autism spectrum disorder (ASD) as a neurodevelopmental disorder, the effectiveness of potential therapeutic procedures considering age and sex differences is under serious discussion. The present study aimed to investigate the effect of resveratrol (RSV) on anxiety-like behaviors and social interaction in juvenile and adult rats of both sex in a valproic acid (VPA)-induced autistic-like model. Prenatal exposure to VPA was associated with increased anxiety, also causing a significant reduction in social interaction in juvenile male subjects. Further administration of RSV attenuated VPA-induced anxiety symptoms in both sexes of adult animals and significantly increased the sociability index in male and female juvenile rats. Taken together, it can be concluded that treatment with RSV can attenuate some of the harsh effects of VPA. This treatment was especially effective on anxiety-like traits in adult subjects of both sexes regarding their performance in open field and EPM. We encourage future research to consider the sex and age-specific mechanisms behind the RSV treatment in the prenatal VPA model of autism.

The effect of early handling on anxiety-like behaviors of rats exposed to valproic acid pre-and post-natally.

INTRODUCTION: Autism spectrum disorder (ASD) is a complex, behaviorally defined disorder of the immature brain as a result of genetic and environmental risk factors, such as prenatal exposure to valproic acid (VPA). This syndrome is known for its high prevalence. On the other hand, postnatal manipulations have been shown to affect brain development, cortical neuroscience, and pituitary-adrenal activity. In early handling (EH) procedure, pups are removed from their mother on a daily basis from birth to lactation, are physically touched, and exposed to the (a) new environment. In the present study, the effect of EH on anxiety-like behaviors in rats exposed pre- and post-natally to valproic acid was investigated. METHODS: Pregnant Wistar rats were randomly separated into six groups which are prenatal saline, Prenatal VPA, Prenatal VPA + EH and postnatal saline, Postnatal VPA, Postnatal VPA + EH. VPA administration was performed either on ED12.5 (600 mg/kg, i.p.) or PD 2-4 (400 mg/kg, s.c.). In the groups receiving EH, pups underwent physical handling from PD 1 to 21. On postnatal day 21 all offspring were weaned and the behavioral tests were performed on 30 and 31 days of age. Elevated plus maze and open field tests were used to investigate anxiety-like behaviors. RESULTS: The results revealed that intraperitoneal injection of valrpoic acid (600 mg.kg) during pregnancy significantly reduced OAT% in males (p < 0.01) and females in a non-significant manner (p > 0.05). In comparison, rearing counts of prenatal VPA groups significantly increased in female sex (p < 0.05) in the EPM test. Following postnatal VPA administration (400 mg/kg), decrease in the time spent in central zone occurred in female rats in the open filed (p < 0.05), as well as a significant increase in the number of grooming of the male sex (p < 0.05). Applying Early Handling to male and female Wistar rats receiving prenatal VPA significantly reversed the OAT% fall (p < 0.05). EH in postnatally VPA exposed animals significantly decreased the OAT% and OAE% criteria, while increasing the locomotor activity of the female sex (p < 0.05). Compared with the postnatal VPA group, no significant change was reported in the EPM performance of postnatal VPA + EH group in neither of sexes (p > 0.05). CONCLUSION: The findings of this study suggest that injections of valproic acid during pregnancy lead to anxiety-like behaviors in male offspring, which EH can improve (attenuate) to some extent. VPA injections on the second to the fourth day of infancy did not have a profound effect on anxiety level. Further behavioral studies need to be performed using other devices to investigate anxiety-like behaviors and to determine the mechanisms involved in these behaviors.

Pathogenesis of COVID-19; Acute Auto-inflammatory Disease (Endotheliopathica & Leukocytoclastica COVIDicus).

BACKGROUND: The pathogenesis of the COVID19 pandemic, that has killed one million nine hundred people and infected more the 90 million until end of 2020, has been studied by many researchers. Here, we try to explain its biological behavior based on our recent autopsy information and review of literature. METHODS: In this study, patients with a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) result were considered eligible for enrollment. Histopathological examinations were done on 13 people who were hospitalized in Afzalipour hospital, Kerman, Iran. Clinical and laboratory data were reviewed. Tissue examination was done by light microscopy, immunohistochemistry and electron microscopy. RESULTS: The most frequent co-morbidity in the patients was cardiovascular disease. The common initial symptoms of COVID-19 infection were dyspnea and cough. In all cases, the number of white blood cells was higher than the normal range. Common histopathological findings were variable degrees of vasculitis as degenerative to necrotic changes of endothelium and trafficking of inflammatory cells in the vessel wall with fibrinoid necrosis. Tissue damage included interstitial acute inflammatory cells reaction with degenerative to necrotic changes of the parenchymal cells. CD34 and Factor VIII immunohistochemistry staining showed endothelial cell degeneration to necrosis at the vessel wall and infiltration by inflammatory cells. Electron microscopic features confirmed the degenerative damages in the endothelial cells. CONCLUSION: Our histopathological studies suggest that the main focus of the viral damage is the endothelial cells (endotheliopathica) in involved organs. Also, our findings suggest that degeneration of leukocytes occurs at the site of inflammation and release of cytokines (leukocytoclastica) resulting in a cytokine storm.

Immunopathology of anthroponotic cutaneous leishmaniasis and incidental diagnostic tool of metastatic granuloma: A case-control study.

BACKGROUND: Cutaneous leishmaniasis (CL) is a neglected disease with important public health concerns in many parts of the world including Iran. OBJECTIVES: We aimed to explore the histological changes and immunohistochemical quantification of inflammatory cells and their role in the immunopathology of acute, chronic non-lupoid, and chronic lupoid skin lesions in anthroponotic CL (ACL). METHODS: In this study, skin biopsies of 53 patients with ACL were taken. Samples were studied by light microscopy and immunohistochemistry to quantify the immune and inflammatory cells. RESULTS: Of the 53 skin lesions, 38 were acute, nine chronic non-lupoid and six chronic lupoid. CD68+ macrophages were the most common cells. CD3+ T-lymphocytes were present as diffuse and focal dermal infiltrates and CD8+ cytotoxic T-lymphocytes were the dominant lymphocyte type, constituting more than 50% of the lymphocyte population. CD4+ T-lymphocytes in chronic non-lupoid (10.57 ± 2.37%) and chronic lupoid (14.40 ± 1.28%) lesions were more than those observed in the acute form (8.61 ± 1.31%), but the differences were not statistically significant. CD20+ B-lymphocytes constituted a small percentage of inflammatory cell infiltrates. CD1a + Langerhans cells showed progressively higher percentages from acute to chronic non-lupoid to chronic lupoid lesions. The differences were statistically significant (P < 0.05) between acute and chronic lupoid lesions. CD68+ macrophages were the most common cells and CD8+ T lymphocytes remained the predominant T-lymphocytes in acute, chronic non-lupoid, and chronic lupoid lesions, suggesting their central role in the pathogenesis and possible healing of CL. CONCLUSION: Focusing on the deep dermis, periadnexal and/or peripheral margins or even papillary tip of inflammatory sites of sandfly bites, we sometimes find granuloma inside lymphatic vessels (lymphangiectatic metastatic granuloma) or even infected macrophages with engulfed Leishman bodies faraway. Knowledge of the histopathological and immunohistochemical findings for various forms of ACL is essential in improving clinical and medical strategies and crucial for proper prophylactic and therapeutic plans.

Prenatal pregabalin is associated with sex-dependent alterations in some behavioral parameters in valproic acid-induced autism in rat offspring.

This study was performed to evaluate the effects of prenatal exposure to pregabalin (PGB) on behavioral changes of rat offspring in an animal model of valproic acid (VPA)-induced autism-like symptoms. Pregnant rats received VPA (600 mg/kg/i.p.) once at 12.5 gestational days for autism-like symptom induction in offspring. After the delivery single male and single female offspring from each mother were randomly selected for behavioral test (anxiety, pain response, pleasure, and motor function) at 60th day adulthood (n = 7). Offspring received prenatal PGB (15 & 30 mg/kg/i.p.) during gestational days 9.5 to 15.5 either alone or in combination with VPA (PGB15, PGB30, PGB15 + VPA, and PGB30 + VPA). Control offspring received normal saline during the same period. The result showed that prenatal VPA exposure was associated with autism-like behaviors in rat offspring. PGB treatment during the gestational period revealed significant reduction in sucrose preference test and anxiety in elevated plus maze and open field test in offspring. Also, PGB treatments exhibited a dose-dependent increase in pain threshold in prenatally VPA exposed rats in tail-flick and hot plate test. Also, there was a sex-related significant impairment in motor function in beam balance and open field test, and male rats were affected more than females. However, no significant sex differences in sucrose preference and pain sensitivity were observed in prenatal PGB-treated rat offspring. In conclusion, prenatal exposure to VPA increased the risk of autism-like behaviors in the offspring rats, and PGB treatment during the gestational period was associated with some beneficial effects, including anxiety reduction and motor impairment in autism-like symptoms in rat offspring.

Efficacy of microneedling plus topical 4% tranexamic acid solution vs 4% hydroquinone in the treatment of melasma: A single-blind randomized clinical trial.

BACKGROUND: There are various treatment modalities for melasma, but none of them are effective on dermal component of melasma. AIMS: In this study, we decided to evaluate the efficacy of microneedling plus tranexamic acid in comparison with 4% hydroquinone in the treatment of melasma. METHODS: This is a single-blind randomized clinical trial on 70 participants with 14% dropout, and therefore, 60 patients with melasma completed the study. Patients were randomized based on simple randomization in 2 groups of A (microneedling plus topical 4% tranexamic acid, monthly) and B (topical 4% hydroquinone, nightly). Evaluation of mean MASI score, patient and physician assessments was performed at 4th, 8th and12th weeks of the treatment. Statistical analysis was performed by paired t test, chi-square test and Fisher's exact test, respectively. RESULTS: Sixty women (30 patients in each group) were completed the study. Mean MASI score in group A was significantly lower at the end of the treatment (6.84 ± 4.31) than at the baseline (12.89 ± 5.16) (P < .01). Mean MASI score in group B was significantly lower at the end of the treatment (7.16 ± 4.38) than at the baseline (13.56 ± 4.88) (P < .01). There was no statistical difference between 2 groups regarding MASI score, physician and patient assessments during the treatment. Percentage of patient satisfaction was significantly higher than physician satisfaction in both treatment groups (P < .01). CONCLUSION: In our study, the combination of microneedling with tranexamic acid did not differ from 4% hydroquinone in the treatment of melasma.

Evidence for antinociceptive effects of combined administration of vitamin E and celecoxib in tail-flick and formalin test in male rats.

BACKGROUND: The aim of this study was to evaluate the effect of vitamin E co-administration with celecoxib in thermal and inflammatory pain in two model of pain assessment including thermal tail flick test of acute pain and formalin induced inflammatory model in adult male rats. METHODS: Seventy two male Wistar rats were divided into a vehicle received intraperitoneally olive oil, indomethacin (20 mg/kg), vitamin E (100, 200 and 400 mg/kg), celecoxib (3, 10, 30 and 60 mg/kg) groups, and combination groups received the combination of vitamin E (100 and 200 mg/kg) and celecoxib (3, 10 and 30 mg/kg). All drugs were dissolved in olive oil. Antinociceptive effect in tail-flick was measured using Area Under Curve (AUC) of responses and Maximum Possible Effect (%MPE) and pain score was used for antinociceptive response in formalin test. RESULTS: Vitamin E and celecoxib changed time course of pain scores in a dose related manner in formalin test but not in tail-flick test. Vitamin E (200 mg/kg) had no effect and merely 60 mg/kg of celecoxib increased %MPE and AUC in tail-flick. The combination of vitamin E (100 or 200 mg/kg) with celecoxib (3 or 10 mg/kg) decreased pain scores compared to vehicle in both phases of formalin test, while in chronic phase (II) the pain scores of combination groups were also decreased compared to vitamin E and celecoxib. However, in tail-flick test the combination of ineffective doses of vitamin E (200 mg/kg) and celecoxib (10 and 30 mg/kg) increased %MPE and AUC compared to vehicle but not compared to celecoxib or vitamin E. CONCLUSIONS: Vitamin E and celecoxib showed a dose related antinociceptive effect in inflammatory but not in thermal model of acute pain. However the co-administration of vitamin E with celecoxib caused a significant increase in the antinociceptive effect which was similar to indomethacin, as a standard anti-inflammatory drug. So we suggest the concomitant use of vitamin E with celecoxib and other NSAIDs for potentiation of both anti- inflammatory and analgesic response, as well as the reduction of cardiovascular side effects of celecoxib.

The Significance of the Stromal Response in Breast Cancer: An Immunohistochemical Study of Myofibroblasts in Primary and Metastatic Breast Cancer.

BACKGROUND: Gene expression profiling of breast cancer has demonstrated the importance of stromal response in determining the prognosis of invasive breast cancer. The host response to breast cancer is of increasing interest to pathologists and may be a future focus for novel pharmacological treatments. METHODS: This study describes the pattern of distribution of stromal myofibroblasts using immunostains for CD10 and smooth muscle actin (SMA) in 50 primary breast cancers and their matched nodal metastases (68.6% nodes positive and 31.4% nodes negative). The stroma within the tumor (intratumoral) and at the advancing tumor edge (peri-tumoral) was studied in both primary and nodal sites. A simple quantitative scoring system was employed for both immunostains. The correlation between expression of these markers by stromal cells and standard pathological prognostic factors of stage, grade, hormone receptor and Her-2 status was analysed. RESULTS: SMA-positive stromal cells were more abundant in peri-tumoral stroma compared with intratumoral stroma in both primary and metastatic lesions. SMA expression in the lymph node metastases showed a significant correlation with tumor stage. SMA expression in peri-tumoral stroma correlated with Her-2 status. CONCLUSION: The results of this study suggest that myofibroblasts, particularly those expressing SMA, might potentiate the progression of the carcinomatous process especially in nodal metastases. Thus these cells may be a potential therapeutic target.

Effects of pregabalin on brain edema, neurologic and histologic outcomes in experimental traumatic brain injury.

Brain edema and increased intracranial pressure (ICP) are among the main causes of neurological disturbance and mortality following traumatic brain injury (TBI). Since pregabalin neuroprotective effects have been shown, this study was performed to evaluate the possible neuroprotective effects of pregabalin in experimental TBI of male rats. Adult male Wistar rats were divided into 4 groups: sham, vehicle, pregabalin 30 mg/kg and pregabalin 60 mg/kg. TBI was induced in vehicle and pregabalin groups by Marmarou method. Pregabalin was administered 30 min after TBI. Sham and vehicle groups received saline. Brain water and Evans blue content and histopathological changes were evaluated 24, 5 and 24 h after TBI, respectively. The ICP and neurological outcomes (veterinary coma scale, VCS) were recorded before, 1 h and 24 h post TBI. The results showed a significant reduction in brain water content and ICP, and a significant increase in VCS of pregabalin group (60 mg/kg) as compared to vehicle group (P < 0.05). Also, pregabalin reduced brain edema and apoptosis score as compared to vehicle group. Post TBI pregabalin administration revealed a delayed but significant improvement in ICP and neurological outcomes in experimental TBI. The underlying mechanism(s) was not determined and needs further investigation.

Possible Interrelationship of Inflammatory Cells in Dry Type Cutaneous Leishmaniasis.

BACKGROUND & OBJECTIVE: There is a complicated interaction between leishmaniasis and the host immune cells, and also between the host immune cells. These interactions have fundamental effects on the outcome of the disease.The current study aimed at characterizing the number, distribution, co-localization, and interrelation of 4 types of inflammatory cells in different clinical forms of dry-type cutaneous leishmaniasis (CL). METHODS: Thirty-nine cases of CL were studied. The cases were classified clinically as 14 cases of acute leishmaniasis with indurated papules, nodules, and plaques with central crust formation < 2 years, 7 cases of chronic type with non-healing lesions > 2 years, and 12 cases of lupoid leishmaniasis with characteristic papules around previous scars of CL > 2 years. Paraffin-embedded blocks were stained with hematoxylin and eosin (H&E) and also stained immunohistochemically for CD4, CD8, CD68, and CD1a. RESULTS: In acute CL, there was a significant correlation between CD68+ macrophages and CD1a+ epidermal dendritic cells (DCs); the population of CD68+ macrophages and CD1a+ epidermal DCs increased in parallel.In lupoid CL, there was a significant correlation between CD1a+ epidermal DCs, and CD1a+ dermal DCs and population of CD1a+ epidermal DCs; the number of CD1a+ dermal DCs increased in parallel. CONCLUSIONS: The result of the current study could be used as a baseline to design and study the new targeted therapy of synergistic effects of macrophages and DCs to phagocytizing leishmania bodies; and/or suggestion planning of individualizing setup of vaccine by autologous interaction of macrophages and DC in CL.

Molecular pathology and histopathological findings in localized leishmania lymphadenitis.

BACKGROUND: A rare variant of Leishmaniasis is Localized Leishmania Lymphadenitis which has been occasionally reported from south-eastern parts of Iran. So far, no molecular assay has been performed for diagnosing this variety of Leishmaniasis. METHODS: Nineteen lymph node paraffin blocks were collected from 1994 to 2007. Parasite load count and histopathological patterns reported on Hematoxylin-Eosin and Giemsa stained slides.DNA extraction was carried out just on the remaining available 7 lymph node paraffin blocks according to QIAamp DNA FFPE kit instructions. A pair of primers and a probe were designed for rRNA ITS region with Allele ID 6.0 software, followed by real time PCR amplification. RESULT: The most common histopathological pattern was necrotizing granuloma with few Leishman bodies. Parasite load was the highest in submental lymph node (3 ± 1.41 per oil field) which was significantly higher compared to cervical and inguinal nodes (P < 0.05). Absolute load of parasite DNA was detectable in all 7 cases. The positive cases revealed a 201 bpamplicon after electrophoresis of end product which was confirmative for Leishmania tropica. CONCLUSION: Real time PCR revealed Leishmania tropica as the etiologic agent of Localized Leishmania Lymphadenitis. Although this molecular method is a sensitive diagnostic tool, histopathological findings are still important.

Evaluation of Antinociceptive Effect of Pregabalin in Mice and its Combination with Tramadol using Tail Flick Test.

The development of combination therapy is a coherent approach in severe pain treatment. The present study investigated the antinociceptive effect of pregabalin alone and in combination with tramadol in acute pain modeling. Therefore, three groups of male mice received either pregabalin (1 to 400 mg/Kg), tramadol (10 to 80 mg/Kg) or their combination intraperitoneally. Then latency time, maximum possible effect (%MPE) and area under curve (AUC) were calculated in tail flick test. The antinociceptive indexes were significantly increasedin10, 100 and 200 mg/kg ofpregabalin while tramadol showed dose-dependentantinociception (effective dose 50% was 54 to 79 mg/Kg). The antinociceptive effect of 100 mg/Kg of pregabalin (%MPE = 35±4%) was similar to that of 50 mg/Kg of tramadol. The combination of non-analgesic doses (10 mg/Kg) of tramadol and pregabalin did not increase %MPE and AUC, but the co-administration of 30 mg/Kg of tramadol with pregabalin (10 mg/Kg) increased all antinociceptive indexes significantly compared to the controls and with each drug alone. In conclusion, pregabalin showed a comparable antinociceptive effect to tramadol. The increase in analgesic effect was observed after the combination of low analgesic doses of tramadol with pregabalin, while the combination of non-analgesic doses of each drug reversed the interaction to antagonism. Therefore to increase the analgesic effect in pain management, more attention should be paid to respecting right proportion of drug combination. Further studies that specify the mechanism(s) and statement of interaction are needed to expand these findings to clinical applications.

Assessment of the antinociceptive effects of pregabalin alone or in combination with morphine during acetic acid-induced writhing in mice.

Visceral pain currently represents one of the most important pain treatment challenges in clinical practice, and investigators across the world are continuously designing and conducting numerous studies in search of new analgesics and new combination therapies. The current study assessed the analgesic effects of saline, pregabalin (2, 5, 17, 50, 100, and 200 mg/kg, i.p.) and morphine (0.25, 0.5, 1, 3 and 5 mg/kg) alone or in combination on acetic-acid induced abdominal contractions in mice. The number of writhes and the inhibitory effects (as percentages, %E) were calculated as antinociception indexes. These indexes indicated that both pregabalin (Prg) and morphine (Mrp) produced dose-dependent antinociception. Pregabalin at 5 mg/kg (%E=32.5±4.0) or 2 mg/kg (%E=20.8±4.5) and morphine at 0.25 mg/kg (%E=20.2±7.8) and 0.5 mg/kg (%E=43.6±4.5) exhibited antinociceptive effects, and the combination of pregabalin and morphine produced significantly greater antinociceptive effects (%E=62.4±5.8 for Prg5+Mrp0.25; %E=71.7±4.8 for Prg5+Mrp0.5; and %E=54.1±4.0 for Prg2+Mrp0.25), although this enhancement was not observed when morphine was combined with 17 mg/kg pregabalin. Pre-treatment with 2 mg/kg (i.p.) naloxone did not affect increased analgesia when combined with these drugs. A dose-response curve was established for pregabalin at a fixed morphine dose and revealed that, at low doses, pregabalin dose-dependently enhanced the antinociceptive effects, while the opposite was true at high doses (17 and 25 mg/kg). In conclusion, pregabalin can produce levels of antinociception that are similar to those of morphine in acetic acid-induced viscero-somatic pain. The enhancement of antinociception produced by the co-administration of morphine and pregabalin is termed a supra-additive interaction and occurred at low doses but not at high doses. These findings militate for increased attention and caution in clinical settings.

Relative potency of pregabalin, gabapentin, and morphine in a mouse model of visceral pain.

PURPOSE: Pregabalin is probably more effective than prototype gabapentin in different kinds of pain treatments. This study was performed to compare the potency of gabapentin, pregabalin, and morphine in a well-established model of visceral pain. METHODS: The number of abdominal contractions was counted for 30 min in adult male mice that received different doses of pregabalin, gabapentin, morphine, or placebo intraperitoneally 30 min before receiving 0.6% acetic acid 10 mL·kg(-1).The antinociceptive effect of each drug dose was determined as a percentage of the reduction in the number of acetic acid-induced writhes. The effective doses, for 20%, 50%, and 80% response (ED(20), ED(50), and ED(80), respectively), of each drug were calculated using least squares linear regression analysis, and then dose-response curves were compared. RESULTS: Pregabalin, gabapentin, and morphine produced a linear dose-dependent antinociceptive effect (coefficient of determination [r(2)] > 0.9). No difference was observed between slopes of dose-response curves. The ED(50) estimates (95% confidence interval) for pregabalin, gabapentin, and morphine were 17.1 (12.9 to 22.1) mg·kg(-1), 87.1 (45.8 to 129.8) mg·kg(-1), and 0.2 (0.1 to 0.3) mg·kg(-1), respectively. CONCLUSION: In this animal model of visceral pain, all three drugs exhibited parallel dose-response curves. Pregabalin had five times the potency of gabapentin and 1/85(th) the potency of morphine. Similar potency ratios may apply in clinical practice. Despite some limitations of animal studies, this model could be useful for comparing new analgesics in visceral pain treatment.

Comparative histological and immunohistochemical changes of dry type cutaneous leishmaniasis after administration of meglumine antimoniate, imiquimod or combination therapy.

BACKGROUND: This study compared histological and immunohistochemical changes of cutaneous leishmaniasis treated with meglumine antimoniate, imiquimod, and the combination of both therapies. METHODS: Single blind clinicopathological studies of fifteen patients with old world cutaneous leishmaniasis in Kerman, Iran were included. A total of four patients received a combination of imiquimod (5% cream) and intra-lesional meglumine antimoniate weekly for four weeks. Monotherapy with imiquimod was given to seven patients and four patients were treated with meglumine antimoniate intralesionally. Histological confirmation was performed before and during therapy. Semi-quantitative histological parameters such as numbers of mixed inflammatory cells (cells/mm(2)) and percentages of Langerhans cells (CD1a+), T-cells (CD3+), B-cells (CD20+), and macrophages (CD68+) were calculated immunohistochemically in the dermis and adjacent epidermis. RESULTS: Topical imiquimod significantly reduced mean histiocytic cellular aggregation size (P<0.05). Meglumine antimoniate reduced parasite load and infected activated histiocytes in the dermis (P<0.05). Meglumine antimoniate therapy decreased epidermal CD3+ lymphocytes but increased them in the dermis, within the granulomas (P<0.05). During topical application of imiquimod a depletion of CD1a+ dendritic cells in the epidermis (P<0.05) and slight predominance of dendritic cells in the dermis were observed. Combined therapy and imiquimod monotherapy decreased CD68+ macrophages in the dermis (P<0.05). CONCLUSION: Meglumine antimoniate decreases parasite load with considerable effect on up-regulation of T-cells, which demonstrates that meglumine antimoniate works as parasitocidal and immunomodulator, which could be a first line of treatment. Imiquimod accentuates the host immune response and reduces granuloma size which could be effective immunomodulator for combination therapy. Monotherapy of imiquimod is less effective than the two other regimens in decreasing parasite load, inflammation and congestion at the inoculated site.

The study of substructures of addiction phenomena in high school students using problem finding workshops.

BACKGROUND: Addiction is one of the complicated problems in Iranian young population. The social and cultural dimensions of this social disease are less considered. So considering socio-cultural and environmental resources, this study investigated the substructures of addiction according to the viewpoints of high-school students of Kerman, Iran in 2007-2008. METHODS: This qualitative study accomplished in ten high schools through a one-day problem finding workshop and continued until data saturation. The resulted terms and phrases were analyzed by content analysis. To assure about the validity and reliability, the outputs reviewed by workshops participants, and classification and codification of the data were executed separately by two experts. FINDINGS: A total of 212 students, 45.3% girls and 54.7% boys, participated in the study. The students introduced the followings as the addiction substantial fundaments: lack of knowledge, positive attitude and interpretation of addiction as a value, family or friends' habit, economy status, psycho-personality problems and availability. Rules infirmity or non-implementation of the current rules enforcement, geographical status and addiction as a conspiracy were also observed in students' statements. CONCLUSION: The positive attitudes and historical roots of addiction along with the process of changing the values caused the growth of drug addiction in young population which could neutralize the security measures, legislations policy and even the knowledge. Therefore, intensification of personal protective factors and culturalization addressed for improving inner layers of values are recommended.

Immunophenotypic pattern and cytokine profiles of dry type cutaneous leishmaniasis.

BACKGROUND: Dry type localized cutaneous leishmaniasis, one of the most prevalent cutaneous parasitic infections in Kerman Province, is presented as a polarized disease in which cytokine profiles secreted by immune cells play a major role in its presentation. In order to clarify the idea, immunohistochemical study of skin biopsies were performed to elucidate the cytokine release capabilities of immune cells. METHODS: Skin biopsies of acute, chronic nonlupoid, and chronic lupoid recidivans lesions of dry type localized cutaneous leishmaniasis were studied by immunohistochemical staining methods for immunophenotypic patterns (CD4, CD8, CD14, CD19, CD56, CD11a, CD18, CD1a, HLA-DR, CD54) and cytokines (INF-gamma, IL-12, IL-4, TNF-alpha) released by immune inflammatory cells. RESULTS: The descriptive analysis of data showed that the mean percentage of positive immunostained cells of CD4, CD8, and CD14; antigen-presenting cells (CD1a, HLA-DR); and markers of the extravasated positive memory T cells (CD11a, CD18, CD54) are more frequent in lupoid recidivans than in acute active and chronic nonlupoid lesions, in order of frequency. CONCLUSION: Based on the results, it seems that Th1-like response is predominant in acute active form and lupoid recidivans while Th2-like response is predominant in chronic nonlupoid lesions. It seems that lupoid recidivans is a type IV hypersensitivity reaction to the reactivation of hidden antigens.