Preclinical Acute Toxicity Assessment of a Crude Polysaccharide Isolated from the Stem of Solanum Nigrum: A Preliminary Analysis

The polysaccharide isolated from Solanum nigrum was proven to possess an immunomodulatory effect and able to suppress the progression of tumor cells by proxy. However, data on the toxicity profile is still limited. The present preclinical study was conducted to investigate the toxicity potential of the crude polysaccharide sample. The acute toxicity experimental design was adapted from OECD 423 guideline. Nine female BALB/c mice were randomly divided into 3 groups, 3 mice per group (n=3). Mice in group A (first-step treatment) were orally administered with a single treatment of crude polysaccharide sample at concentration 2,000 mg/kg/bw (300 µL). Mice in group B (second-step treatment) were received the single treatment after 24 hours, depending on the observation of mice in group A. Mice in group C served as control. Mortality and clinical signs associated with toxicity were observed within 24 hours of treatment session and for the subsequence 14 days for delay-death detection. Mice body weight was recorded starting at day-0 until day-14 prior to sacrificing at day-15. Blood, liver, and kidney were harvested for toxicology assessment. Within 24 hours of treatment, 1 mouse in group A was found to died, while no mortality and delay-death were observed in groups B and C. Referring to OECD 423, it was estimated that the LD50 of the treated sample was 2,500–5,000 mg/kg/bw. No significant changes (p<0.05) were detected in terms of body weight and organ weight indexes of the treated mice as compared to control. The polysaccharide treatment also revealed no significant elevation in mice serum glucose levels. The present findings indicated that the treatment of crude polysaccharide sample exerted a very mild acute toxicity effect when orally administered at 2,000 mg/kg/bw, with no delay-death.

Effects of High-Frequency Repetitive Transcranial Magnetic Stimulation on Upper Limb Dystonia in Patients With Wilson's Disease: A Randomized Controlled Trial

Background: Upper limb dystonia is a frequent complication of Wilson's disease (WD). It can lead to poor quality of life and disability. Currently, no effective treatment for it exists. Therefore, we carried out a clinical trial to determine whether high frequency repetitive transcranial magnetic stimulation (rTMS) on the primary motor cortex alleviates upper limb dystonia in WD patients.Methods: This study was a single-center, double-blind, randomized clinical study, included 60 WD patients with upper limb dystonia from a research base of WD in Hefei, China. Participants were randomly divided into a treatment group (TG) and a control group (CG). The TG received rTMS at 10 Hz, while the CG received sham stimulation for 7 consecutive days. Participants were assessed at baseline, after the seventh treatment session, and at 2 and 4 weeks after the seventh treatment session. The primary outcomes included patients' objective muscle tension and stiffness as measured with the MyotonPRO device. The secondary results were scores on clinical scales assessing muscle spasm and motor symptoms, which included the Modified Ashworth Scale (MAS), Unified Wilson's Disease Rating Scale (UWDRS), Burke Fahn Marsden Scale (BFM), and the Activities of Daily Living (ADL) scale.Results: The analysis revealed that after 10 Hz rTMS, muscle tension (P &lt; 0.01) and stiffness (P &lt; 0.01) as measured by the MyotonPRO device decreased significantly in the TG compared to the CG. Moreover, clinically relevant scale scores, including the MAS (P &lt; 0.01), UWDRS (P &lt; 0.01), BFM (P &lt; 0.01), and ADL (P &lt; 0.01) were also significantly reduced.Conclusion: High-frequency rTMS over the primary motor cortex may be an effective complementary and alternative therapy to alleviating upper limb dystonia in WD patients.Clinical Trial Registration:http://www.chictr.org.cn/, identifier: ChiCTR2100046258.

Does the Score on the MRC Strength Scale Reflect Instrumented Measures of Maximal Torque and Muscle Activity in Post-Stroke Survivors?

It remains unknown whether variation of scores on the Medical Research Council (MRC) scale for muscle strength is associated with operator-independent techniques: dynamometry and surface electromyography (sEMG). This study aimed to evaluate whether the scores of the MRC strength scale are associated with instrumented measures of torque and muscle activity in post-stroke survivors with severe hemiparesis both before and after an intervention. Patients affected by a first ischemic or hemorrhagic stroke within 6 months before enrollment and with complete paresis were included in the study. The pre- and post-treatment assessments included the MRC strength scale, sEMG, and dynamometry assessment of the triceps brachii (TB) and biceps brachii (BB) as measures of maximal elbow extension and flexion torque, respectively. Proprioceptive-based training was used as a treatment model, which consisted of multidirectional exercises with verbal feedback. Each treatment session lasted 1 h/day, 5 days a week for a total 15 sessions. Nineteen individuals with stroke participated in the study. A significant correlation between outcome measures for the BB (MRC and sEMG p = 0.0177, ρ = 0.601; MRC and torque p = 0.0001, ρ = 0.867) and TB (MRC and sEMG p = 0.0026, ρ = 0.717; MRC and torque p = 0.0001, ρ = 0.873) were observed post intervention. Regression models revealed a relationship between the MRC score and sEMG and torque measures for both the TB and BB. The results confirmed that variation on the MRC strength scale is associated with variation in sEMG and torque measures, especially post intervention. The regression model showed a causal relationship between MRC scale scores, sEMG, and torque assessments.

Racemic ketamine as an alternative to electroconvulsive therapy for unipolar depression. A randomized, open-label, non-inferiority trial. (KetECT)

BACKGROUND Ketamine has emerged as a fast-acting and powerful antidepressant, but no head to head trial has been performed, Here, ketamine is compared to electroconvulsive therapy (ECT), the most effective therapy for depression. METHODS Hospitalized patients with unipolar depression were randomized (1:1) to thrice-weekly racemic ketamine (0.5 mg/kg) infusions or ECT, in a parallel, open-label, non-inferiority study. The primary outcome was remission (Montgomery Åsberg Depression Rating Scale [MADRS] score ≤10). Secondary outcomes included adverse events (AEs), time to remission and relapse. Treatment sessions (maximum of twelve) were administered until remission or maximal effect was achieved. Remitters were followed for twelve months after the final treatment session. RESULTS 186 inpatients were included and received treatment. Among patients receiving ECT 63% remitted, compared to 46% receiving ketamine infusions (p=0.026; difference 95% CI 2%, 30%). Both ketamine and ECT required a median of six treatment sessions to induce remission. Distinct adverse events (2015) were associated with each treatment. Serious and long-lasting AE, including cases of persisting amnesia, were more common with ECT, while treatment emergent AE led to more dropouts in the ketamine group. Among remitters, 70% and 63%, with 57 and 61 median days in remission, relapsed within twelve months in the ketamine and ECT group respectively (p=0.52). CONCLUSION Remission and cumulative symptom reduction following multiple racemic ketamine infusions in severely ill patients (age 18-85) in an authentic clinical setting suggest that ketamine, despite being inferior to ECT, can be a safe and valuable tool in treating unipolar depression.

Treating chronic migraines with botulinum toxin

Migraine is a common condition that causes significant morbidity. It is often divided into acute and chronic, but there can be overlap between those who have variable frequency acute episodes and those who have chronic migraine with 15 headache-associated days per month. Botulinum toxin is a prophylactic treatment licensed for chronic migraine, where it has been shown to be an effective and safe treatment. It requires approximately 200 units per treatment session, usually at 3-month intervals. The protocols allowing NHS treatment strictly limit its use. Patients may seek this on a private basis, and suitably qualified aesthetic clinicians who are Care Quality Commission-registered could reasonably treat patients.

Feasibility of an adjunctive cognitive task in the treatment of posttraumatic stress disorder

Visuospatial cognitive tasks that influence memory reconsolidation may be of benefit in reducing intrusive memories for traumatic events when used as an adjunct to trauma-focused psychotherapy. We conducted a feasibility assessment of a protocol that involved the use of a visuospatial cognitive task, the Tetris intervention, alongside routine exposure-based treatment for posttraumatic stress disorder (PTSD). Participants were inpatients attending for PTSD treatment at a psychiatric hospital. The Tetris intervention was administered on three occasions when imaginal exposure had formed part of the treatment session. Using a phone app, participants also monitored intrusive memories over a 3-week period. Feasibility outcomes were fully met for the demand, implementation, practicality and adaptability criteria. Only a single criterion was not met for each of the acceptability and implementation criteria. Limited-efficacy testing outcomes are also discussed. Overall, the findings from our feasibility study indicated viability of the protocol, which involved implementation of the Tetris intervention alongside routine exposure-based treatment for PTSD, in a clinical inpatient setting.

Analysis of Clinical Research Trends for Acupotomy Treatment of Peripheral Facial Palsy

The purpose of this review was to investigate acupotomy treatment for peripheral facial palsy. By reviewing recent clinical trends, this may contribute to standardizing acupotomy treatment methods. There were 7 randomized controlled trials and 6 case series using acupotomy treatment for peripheral facial palsy published between January 01, 2014 and April 05, 2021, which were retrieved from 9 online databases. The number and characteristics of participants, main treatment sites, combination treatments, size of acupotomy needle, frequency and total period of treatment, evaluation indices, efficacy, and adverse events were analyzed. “Tender point or induration,” “infraorbical foramen,” and “buccal mucosa” were the most used treatment sites. The sizes of acupotomy needles varied from 20 mm to 80 mm in length, and 0.35 mm to 1.0 mm in diameter. One treatment cycle was performed every 3 to 5-7 days, and the number of treatments per treatment session ranged from 3 to 5-9 cycles. The results were evaluated using 1 to 4 evaluation indices and 9 different evaluation indices were used overall. The efficacy rate was the most used index, followed by the House-Brackmann grade, and electrocardiography. The “Risk of Bias 2,” categorized most studies as having “some concerns.” There were few adverse events reported.

A Case Report of Vitiligo Induced by Alexandrite Hair Removal Laser

Vitiligo is one of the disorders where we usually see Koebner lesions. Lasers target a chromophore in the skin to deliver their energy. Their effect is theoretically considered as injury and may induce Koebner lesions in vitiligo patients. Few cases were reported with the different kinds of laser, including laser hair removal (LHR). No cases have ever been reported of vitiligo lesions induced by Alexandrite LHR. Here we present a case report of a young female patient who had never had vitiligo until she received a 755-nm LHR treatment. These vitiligo lesions were completely treated with NB-UVB with no recurrence until 4 years later when she received another 755-nm LHR treatment session with a different machine, which lead to new vitiligo patches only on the areas that received the laser.

The role of dopamine D₂ receptor mechanisms in the development of MDMA sensitisation

<p>Rationale. ±3, 4-methelynedioxymethamphetamine (MDMA) is the primary psychoactive ingredient of the increasingly popular recreational street drug, ecstasy. As with other drugs of abuse, repeated intermitted exposure to MDMA can lead to an increase in the subsequent behavioural effects of the drug. This phenomenon, termed behavioural sensitisation, has been attributed to sensitisation of central DAergic mechanisms considered to underlie several aspects of addiction. Objectives. The purpose of the present research was to investigate the role of DA D₂ receptor mechanisms in the development of MDMA sensitisation and the acquisition of MDMA self-administration in rats. Methods. Rats received daily i.p. injections of the selective D₂ antagonist, eticlopride (0.0, 0.05, 0.3 mg/kg), prior to injections of MDMA (0.0, 10.0 mg/kg) for five days. Two days following the final pre-treatment session, the locomotor activating effects of MDMA (5 mg/kg, i.p.) were determined. Another group of rats were surgically implanted with i.v. jugular catheters before undergoing the same pre-treatment regimen. Two days following the final pre-treatment session, these rats were subsequently tested for acquisition of MDMA self-administration. The locomotor activating effects of MDMA (5 mg/kg i.p.) were determined two days following the last self-administration session. Results. Pre-treatment with MDMA enhanced the locomotor activating effects of MDMA and facilitated the acquisition of MDMA self-administration, as evidenced by an increased likelihood to meet an acquisition criterion. Co-administration of eticlopride during pre-treatment completely blocked the development of sensitisation to MDMA-produced hyperactivity but failed to significantly attenuate the facilitation of MDMA self-administration. Interestingly, pre-treatment with eticlopride alone also facilitated the acquisition of self-administration. MDMA self-administration failed to alter MDMA-produced locomotor hyperactivity. Conclusions. These findings suggest that repeated activation of DA D₂ receptors is required for the development of sensitisation to MDMA-produced hyperactivity but not for the development of sensitisation to MDMA-produced reinforcement. D₂ receptor mechanisms evidently play some role, however, because repeated exposure to eticlopride also facilitated MDMA self-administration. It is suggested that both sensitised DAergic mechanisms and desensitised 5-HTergic mechanisms contribute to the acquisition of MDMA self-administration.</p>