The role of fractional laser-assisted drug delivery in enhancing the efficacy of topical bimatoprost solution in the treatment of alopecia areata: An intra-patient comparative randomized clinical trial.

BACKGROUND: Transepidermal drug delivery is a novel therapeutic technique to boost efficacy of topical drugs. AIM: In this clinical trial we evaluate the efficacy of the combination of fractional carbon dioxide (FCO2) laser and bimatoprost solution compared to bimatoprost alone in the treatment of alopecia areata. METHODS: This is a prospective intra-patient comparative randomized clinical trial on 20 patients with alopecia areata. In each participant two patches were chosen to randomly receive either topical 0.03% bimatoprost solution (twice a day for 12 weeks) alone or in combination with FCO2 laser (every 2 weeks for 12 weeks). Then response to treatment was evaluated by the measurement of the severity of alopecia tool score system (SALT) score, percentage of hair regrowth, physician assessment and patients' satisfaction. RESULTS: SALT score was reduced significantly during treatment sessions and after a 3-month follow-up in both treatment groups (p = 0.000). The mean percentage of improvement in SALT score in the combination therapy and monotherapy groups were 46.43 ± 4.35% and 21.16 ± 4.06% at the end of the study and 46.42 ± 5.75% and16.11 ± 3.10% at the end of the follow-up period, respectively (p = 0.000). A general linear model of two-way analysis demonstrated a significantly superior outcome in the combination therapy group compared to the monotherapy group during time (F1.6, 13.2 = 43.8. p = 0.000). CONCLUSION: Fractional ablative laser can be considered as an assistant method for enhancing of efficacy of topical drugs especially in refractory cases of patchy alopecia areata.

High-Intensity Interval Training-Induced Hippocampal Molecular Changes Associated with Improvement in Anxiety-like Behavior but Not Cognitive Function in Rats with Type 2 Diabetes.

(1) Background: Exercise exerts many neuroprotective effects in diabetes-induced brain disorders. In this study, we investigated the effect of high-intensity interval training (HIIT) on brain molecular changes and cognitive and anxiety-like behaviors in rats with type 2 diabetes. (2) Methods: Twenty-eight adult male rats were divided into four groups (n = 7): control (C), exercise + control (C+EX), diabetes (DM), and diabetes + exercise (DM+EX). Diabetes was induced using a two-month high-fat diet and a single dose of streptozotocin (35 mg/kg) in the DM and DM+EX groups. After, the C+EX and DM+EX groups performed HIIT for eight weeks (five sessions per week, running at 80-100% of VMax, 4-10 intervals) on a motorized treadmill. Then, the elevated plus maze (EPM) and open field test (OFT) were performed to evaluate anxiety-like behaviors. The Morris water maze (MWM) and shuttle box were used to assess cognitive function. The hippocampal levels of beta-amyloid and tau protein were also assessed using Western blot. (3) Results: The hippocampal levels of beta-amyloid and tau protein were increased in the DM group, but HIIT restored these changes. While diabetes led to a significant decrease in open arm time percentage (%OAT) and open arm enters percentage (%OAE) in the EPM, indicating anxiety-like behavior, HIIT restored them. In the OFT, grooming was decreased in diabetic rats, which was restored by HIIT. No significant difference between groups was seen in the latency time in the shuttle box or for learning and memory in the MWM. (4) Conclusions: HIIT-induced hippocampal molecular changes were associated with anxiety-like behavior improvement but not cognitive function in rats with type 2 diabetes.

Changes of Routine Hematological Parameters in COVID-19 Patients: Correlation with Imaging Findings, RT-PCR and Outcome.

BACKGROUND & OBJECTIVE: Coronavirus disease 2019 (COVID-19) is progressively spreading, and many researchers have focused on the prognostic value of laboratory analyses. This study reviewed routine blood parameters, upper respiratory viral load, and chest imaging in recovered and expired COVID-19 patients and evaluated possible correlations. METHODS: In this retrograde study, 138 COVID-19 cases were enrolled. Chest tomography scores of patients, routine hematologic and biochemical parameters, and respiratory viral loads were measured. Furthermore, their correlation with severity of disease and the outcome was investigated during a week of admission. RESULTS: The mean age of participants was 58.6±16; 36.2% of whom were diagnosed as critical, 8.7% expired, and 46% showed less than 50% lung opacity. The expiring rate was only correlated to the severity of illness and viral load. During admission, hemoglobin concentration was decreased in critical patients (from 11.49±0.27 to 10.59±0.36, P=0.042) and also among CT-scan scoring groups (P=0.000), while neutrophils (P=0.04), WBC (P=0.03), and platelets (P=0.000) count were increased. In patients with more than 50% lung opacity, leukocyte counts were decreased, but neutrophil and platelets counts showed raise (all P<0.05), while other hematologic parameters did not change. CRP and LDH demonstrated no increase based on the severity of the illness, RT-PCR viral loads and/or outcome. However, both CRP and LDH were increased in patients with more than 50% lobal opacity (CRP: 69.3±9.9 to 1021.1±7.5 and LDH:589.5±93.2 to 1128.6±15.81, P<0.05). CONCLUSION: We found that hemoglobin, white blood cells, neutrophil, lymphocytes, and platelets count together with chest tomography score might be beneficial for expedition the diagnosis, assessmen the severity of the disease, and outcome in the hospitalized cases, while CRP and LDH might be considered as the consequence of lung involvement.

Prenatal Pregabalin Exposure Alters Postnatal Pain Sensitivity and Some Behavioral Responses in Adult Offspring Rats.

BACKGROUND: Prenatal antiepileptic drug exposure could demonstrate both congenital malformations and behavioral impairments in offspring. OBJECTIVE: This study was performed to assess the effects of prenatal exposure to pregabalin (PGB) on pain response, anxiety, motor activity and some behavior of adult offspring rats. METHODS: Pregnant Wistar rats received PGB (7.5, 15 and 30 mg/kg/ip) during embryonic days 9.5- 15.5. The pain response, anxiety-like behaviors, locomotor activity, motor balance and coordination and anhedonia of adult offspring were examined by tail-flick and hot plate test, open field test, elevated plus maze (EPM), beam balance test and sucrose preference test in their 60th day of life, respectively. RESULTS: Prenatal exposure to PGB revealed significant dose-dependent reduction in pain sensitivity (increase in pain latency response) in the hot plate test, especially in females, while anxiety-like behavior assessed in EPM and open field significantly reduced in males. In the open field, locomotor activity reduced significantly after exposure to PGB 30 mg/kg and motor coordination decreased dose-dependently, especially in males. Anhedonia, as an indication of sucrose preference or pleasure response, was not changed. CONCLUSION: These findings suggest that prenatal PGB exposure could be associated with significant changes in pain response, anxiety, locomotor activity and coordination in adult offspring rats.

Sex dependent alterations of resveratrol on social behaviors and nociceptive reactivity in VPA-induced autistic-like model in rats.

INTRODUCTION: The present study was designed to clarify the effects of resveratrol (RSV) on social behavioral alterations and nociceptive reactivity in valproic acid (VPA)-induced autistic-like model in female and male rats. METHODS: Pregnant Wistar rats were randomly divided in five groups. Animals received saline, DMSO, VPA, RSV and RSV + VPA. VPA was administered (600 mg/kg, i. p.) on embryonic day 12.5 (E12.5) and pretreatment by resveratrol (3.6 mg/kg, s. c.) was applied on E6.5 until E18.5. All offspring were weaned on postnatal day 21 and the experiments were done in male and female rats on day 60. Social interaction, hot plate and tail flick tests were set out to assess social deficits and pain threshold, respectively. Sociability index (SI), Social novelty index (SNI) and latency time were calculated as the standard indices of social behaviors and pain threshold, respectively. RESULTS: The results indicated that systemic intraperitoneal administration of VPA (600 mg/kg) significantly decreased SI and SNI in social interaction test (SIT) especially in male rats, indicating the social impairments caused by VPA. RSV (3.6 mg/kg, s. c.) reversed VPA-induced social deficits in male rats, but not in female group. VPA administration resulted in significant increase in latency time in the hot plate and tail flick tests in male rats, whereas it had no such dramatic effect in females. RSV administration in combination with VPA had no significant effect on latency time compared to the valproic acid group in male rats. It is important to note that RSV by itself had no significant effect on SI, SNI and latency time in female and male rats. CONCLUSION: It can be concluded that valproic acid produces autistic-like behaviors and increases pain threshold in male rats which may be ameliorated at least in part by resveratrol administration. Further studies are needed to elucidate the molecular mechanisms involved in valproic acid and resveratrol-induced effects.

The Contribution of NMDA Receptors in Antinociceptive Effect of Pregabalin: Comparison of Two Models of Pain Assessment.

BACKGROUND: Pregabalin has shown remarkable antinociceptive effects in neuropathic pain; however, its efficacy against acute and visceral pain remained controversial. OBJECTIVES: The present study aimed at investigating the involvement of N-methyl-D-aspartate (NMDA) receptors in the antinociceptive effect of pregabalin in both acute and visceral pain using and comparing hot plate test and writhing test in male mice. METHODS: NMDA (15 and 30 mg/kg), as an agonist or MK801 (0.02 and 0.05 mg/kg) as an NMDA receptor (NMDAR) antagonist, were injected intraperitoneally either alone or 15 minutes before a dose of pregabalin that produced almost 30% antinociception (100 mg/kg in hot plate test and 5 mg/kg in writhing tests). Then, the percentage of maximal possible effect (MPE%) at the 30th and 60th minutes in hot plate test and effect percentage (E%) in writhing test were measured and compared as antinociceptive indexes. RESULTS: In hot plate test, pretreatment with MK801 (0.05 mg/kg) significantly increased antinociceptive effect of 100 mg/kg pregabalin, but pretreatment with NMDA did not result in any effect. Pretreatment with MK801 in writhing test significantly increased the antinociceptive effect of 5 mg/kg pregabalin (In contrast to 30 mg/kg NMDA that significantly decreased it.). NMDA induced antinociception reduction or MK801 increased antinociception in writhing test were significantly higher than what was observed in hot plate test. CONCLUSIONS: Our results suggested that pregabalin antinociception in acute and visceral pain is mediated through NMDA receptors. Although this effect depends on the dose of NMDAR ligand, it is more pronounced in the behavioral response in the writhing test.

The effects of co-administration of pregabalin and vitamin E on neuropathic pain induced by partial sciatic nerve ligation in male rats.

OBJECTIVE: This study was performed to evaluate the effect of pregabalin co-administration with vitamin E in Partial Sciatic Nerve Ligation (PSNL)-induced neuropathic pain in rats. METHODS: Male Wistar rats were randomly allocated as control, sham, and PSNL groups (n = 8). PSNL was induced by tight ligation of the sciatic nerve with a copper wire. On day 14th, the PSNL and sham operated rats received either pregabalin (1, 3, and 30 mg/kg), vitamin E (100 and 200 mg/kg), or their combination intraperitoneally. An antinociceptive effect was evaluated as latency times and Maximum possible Effect Percent (%MPE) using tail-flick test. Locomotor activity was evaluated by open-field test before PSNL surgery and then twice at the 14th days (before and after drug injection). Ligated nerves were removed on the 28th days after surgery for histological examinations. RESULTS: The time course of latency times and %MPE showed significant decrease in PSNL but not in sham and control groups. Pregabalin (3 and 30 mg/kg) and vitamin E (100 and 200 mg/kg) caused significant increases in latency time in PSNL (but not sham) group compared to control group. Vitamin E 200 mg/kg increased significantly %MPE in PSNL group compared to sham group. In addition, the %MPE following combination treatment of pregabalin (30 mg/kg) and vitamin E (100 mg/kg) was significantly higher than both vitamin E and control group. Also combination of pregabalin with 100 mg/kg of vitamin E reversed Wallerian degeneration of sciatic nerve and the inflammatory responses to almost similar to sham group. Pregabalin and vitamin E did not affect locomotor activity. CONCLUSION: Our results showed antinociceptive effects of both vitamin E and pregabalin alone or in combination in PSNL rats and also neuroprotective properties without affecting locomotor activity.

The Role of NMDARs Ligands on Antinociceptive Effects of Pregabalin in the Tail Flick Test.

BACKGROUND: Pregabalin as a new anticonvulsant has been used in different pain treatments. OBJECTIVES: The aim of this study was to investigate the role of N-methyl-D-aspartate (NMDA) ligands in antinociceptive effect of pregabalin in mice using tail flick. MATERIALS AND METHODS: NMDA (15 and 30 mg/kg) as an agonist or MK801 (0.02 and 0.05 mg/kg) as an antagonist were injected intraperitoneally either alone or 15 minutes before antinociceptive dose of pregabalin (100 mg/kg). Then the latency times and %MPE were measured in the tail flick assay during 75 minutes. RESULTS: NMDA and MK801 had no effects alone. NMDA pretreatment significantly decreased the latency times of pregabalin till 75(th) minutes. In NMDA pretreated groups, %MPE30 unlike %MPE75 decreased significantly compared to those of pregabalin. MK801 delayed the latency times in pretreated groups, but %MPE30 and %MPE75 did not change significantly compared to pregabalin alone. CONCLUSIONS: Our findings support the role of NMDARs in pregabalin antinociception, because the NMDAR agonist, unlike the antagonist, decreased the antinociceptive effect of pregabalin, even if tail flick is not an adequate pain assessment method in this regard.

Serum biochemical parameters following heroin withdrawal: an exploratory study.

BACKGROUND: Long-term consumption of opioid compounds, even after withdrawal, affects serum biochemical parameters. Investigating these alterations is a new approach in substance abuse studies. METHOD: This study investigated clinical laboratory results in men who are currently active, recently abstinent and non-heroin users. Participants (N = 240) of this matched cohort study included heroin dependent men referred for abstinence treatment, volunteer men who did not abuse opioids matched for age, sex, body mass index, and educational level (control group). The groups were further sub-divided for analysis into (a) continuous heroin users for more than 2 years (N = 70), the dependent group; (b) heroin abusers with 1 month abstinence period (N = 70), identified as ex-heroin dependents; and (c) a matched, non-dependent control group (N = 100). All participants were tested for fasting blood sugar (FBS), sodium, potassium, calcium, uric acid (UA), blood urea nitrogen (BUN), creatinine, total cholesterol, triglycerides (TGs), total protein, fibrinogen, and prothrombin. RESULTS: Compared to the control group, ex-heroin dependents showed decreased FBS and significantly higher sodium, creatinine, and cholesterol levels. Compared to the heroin dependent group, the ex-heroin dependents showed significant differences in FBS, sodium, calcium, creatinine, UA, and thrombin time. No significant differences were noted between ex-heroin dependents and controls in potassium, calcium, UA, BUN, TGs, total protein, and thrombin time. CONCLUSION: These results demonstrate altered laboratory markers in long-term heroin dependents as well as ex-heroin dependents and suggest the need for further identification, population distribution, and etiological understanding of these biomarkers in individuals who have abused heroin.

Pregabalin antinociception and its interaction with tramadol in acute model of pain.

BACKGROUND: The aim of present study was to investigate the antinociceptive effect of pregabalin and tramadol either alone and or in combination on acute model of pain. METHODS: The antinociceptive effect of intraperitoneal administration of pregabalin (1 to 400 mg/kg) and tramadol (10 to 80 mg/kg) or combination of them were measured after 30 and 60 min on hot-plate in terms of maximum possible effect (%MPE) in mice. RESULTS: Antinociceptive effect rose significantly for both pregabalin at doses 200 and 400 mg/kg and tramadol from 20 to 80 mg/kg in dose dependent manner. From linear equation the doses that increased antinociceptive effect by 50% (ED(50)) were 69 ± 8.2 mg/kg for tramadol and 246 ± 24 mg/kg for pregabalin. Unlike pregabalin, %MPE(30) (at 30(th) min) of tramadol was significantly higher than its %MPE(60). The interaction after co-administration of non analgesic dose of 10 mg/kg of pregabalin with low analgesic dose of 30 mg/kg of tramadol resulted super-additive and %MPE(30) and %MPE(60) were increased compared to each drug alone. In all other combination groups, the interaction were sub-additive particularly when non analgesic doses of each drug (10 mg/kg) were co-administrated and %MPE was decreased significantly compared to that of each drug alone. CONCLUSION: Pregabalin revealed a comparative antinociceptive effect as similar to tramadol in acute model of pain, but interaction between these two drugs depends highly on their proportion in the combination. The analgesia may increase but adverse effects such as seizurogenic effect of tramadol can be reduced in clinical setting if right proportion is used. More studies are required to understand the mechanisms and clinical implication of such combinations.

Possible association between human blood types and opioid addiction.

Drug addiction is a complex disorder that has been shown to have a genetic component like several other diseases. Finding any factor that is associated with higher risk of addiction tendency may influence the strategies of prevention and treatment of drug abuse and also provide an avenue of further research in genetics, immunology, and other related fields. This case-control study aimed at finding the frequency rate of ABO blood groups and Rhesus (Rh) factor among opioid dependents. Therefore, 249 opioid dependents referred to the Drug Quit center at Bam, Iran (case group) were compared with 360 blood donors referred to the Blood Transfusion Center (control group) in regard to the frequency of blood groups and Rh factor. The two groups were matched for demographic features. The odds ratio for AB blood group in addicts was 3.98 compared to non-addicts (p < .001) and the odds ratio of negative Rh in addicts compared to non-addicts was 4.27 (p < .001). According to the findings, in this population the frequency of negative Rh and AB blood group were significantly less than the predictive values. The relationship between opioid use and blood group type requires a cohort study eliminating all extraneous factors in order to be proved.

Comparison of cytologic giemsa and real-time polymerase chain reaction technique for the diagnosis of cutaneous leishmaniasis on scraping smears.

OBJECTIVE: To compare the results of real-time polymerase chain reaction (RT-PCR) for detection of Leishmania DNA in Giemsa-stained skin scraping slides with direct microscopic evaluation of Giemsa-stained skin scrapings and to estimate the sensitivity and specificity of RT-PCR. STUDY DESIGN: We used 30 samples from cases diagnosed with cutaneous leishmaniasis (CL), 16 from clinically suspected individuals but negative in direct microscopic evaluation and 50 normal individuals from nonendemic dry type CL areas. RESULTS: All samples of CL positive and 8 of suspected cases were positive for RT-PCR, and all nonleishmaniasis cases were negative. The sensitivity and specificity of RT-PCR were 100% (95% CI 88-100%) and 88% (95% CI 78-95%), respectively. We also found an inverse association between the number of lympnocytes (OR = 0.90, 95% CI 0.83-0.97%), neutrophils and Leishman bodies.

Electrophoretic profile of serum proteins in opium and heroin dependents.

OBJECTIVES: In this cross-sectional case-control study, albumin and globulin profile in the serum of opium and heroine addicts have been compared with correspondent values in a matched control group. METHODS: Opioid consumption was confirmed by laboratory diagnostic tests on urine samples and protein electrophoresis of serum was performed to determine the concentration and profile of serum proteins. RESULTS: There was no significant difference in albumin, alpha(1)-globulin, alpha(2)-globulin, and beta-globulin concentration among groups. Gamma-globulin concentration in opium and heroin addicts showed no significant difference, but it was significantly lower in comparison to the control group. CONCLUSION: This finding may be attributed to the higher probability of infectious diseases in opioids addicts.

Gabapentin enhances the analgesic response to morphine in acute model of pain in male rats.

Whenever opioids as drug of choice result in inadequate analgesia, the combinational therapy would be the solution. In this study the co-administration of gabapentin with morphine is evaluated in acute model of pain. Therefore the antinociceptive effect of gabapentin (30 or 90 mg/kg, s.c.) and morphine (0.5, 1 or 3 mg/kg, s.c.) alone or in combination were measured by tail-flick test in intact adult male rats. Control rats received normal saline. Tail-flick latency time and Area Under Curve (AUC), as antinociception index were calculated for each groups. There was not any significant difference between the antinociceptive response of 0.5 mg/kg morphine and 30 mg/kg gabapentin as compared to controls, but co-administration of these subanalgesic doses increased significantly AUC as compared to morphine alone. The co-administration of gabapentin with analgesic doses of 1 and 3 mg/kg morphine had also increased significantly AUC. Therefore gabapentin enhanced the antinociceptive effect of both analgesic and subanalgesic doses of morphine in a dose dependent manner. In conclusion co-administration of gabapentin with low doses of morphine produced therapeutic analgesia which could have important clinical application.