Rehabilitative training following unilateral pyramidotomy in adult rats improves forelimb function in a non-task-specific way

Spontaneous functional recovery following injury to the adult central nervous system can be enhanced with increased and focused activity, either through altered behaviour (skill learning, exercise or training) or by artificial stimulation (magnetic or electrical). In terms of training, the choice of paradigm plays a key role in the recovered behaviour. Here we show that task-specific training leads to improved forelimb function that can be translated to a novel forelimb task. Adult Long–Evans rats received a unilateral pyramidotomy and we studied the effects of different post-lesion training paradigms for their ability to recover function in the impaired limb. We trained rats on either the single pellet grasping or the horizontal ladder task. Rats were tested on both tasks regardless of the training paradigm and also on a related, but novel forelimb task, the Staircase. Horizontal ladder training led to full recovery of this task, and also limited recovery on the familiar but untrained single pellet grasping task. In comparison, single pellet grasping training led to a smaller improvement on the horizontal ladder, but interestingly the same degree of recovery on the single pellet grasping task as horizontal ladder trained animals. Both training groups performed equally well on a novel, untrained forelimb grasping task. These results show that task-specific forelimb training can lead to functional recovery also in non-trained, complex, forelimb movements. Anatomically, only single pellet grasping training was associated with enhanced sprouting of the intact corticospinal tract across the cervical spinal cord midline to innervate the denervated side of the spinal cord.     

Irritable Bowel Syndrome in a Bangladeshi Urban Community: Prevalence and Health Care Seeking Pattern

Background/Aims:

Although irritable bowel syndrome (IBS) is a common gastrointestinal disorder, its prevalence is unknown, especially in the urban population of Bangladesh. This community-based study aimed to find out the prevalence of IBS and healthcare-seeking patterns using the Rome-II definition.

Materials and Methods:

A population-based cross-sectional survey of 1503 persons aged 15 years and above was carried out in an urban community of Bangladesh. The subjects were interviewed using a valid questionnaire based on Rome-II criteria in a home setting. Statistical analysis was performed with Statistical Package for Social Science (SPSS) Programmers and the level of significance was set at P ≤ 0.05.

Results:

A response rate of 97.2% yielded 1503 questionnaires for analysis. The prevalence of IBS was found to be 7.7% (n = 116) with a male to female ratio of 1:1.36 (49 vs. 67). “Diarrhoea-predominant IBS” (50%, n = 58) was the predominant IBS subgroup. Symptoms of abdominal pain associated with a change in stool frequency (100%) and consistency (88.8%) were quite common. All IBS symptoms were more prevalent among women (P < 0.000). In the past one year, 65.5% (n = 76) IBS subjects had consulted a physician with a slightly higher rate of women consulters (68.6 vs. 61.2%). The main predictor for healthcare-seeking was the presence of multiple dyspeptic symptoms.

Conclusions:

The prevalence of IBS in the urban community was found to be similar to that in rural communities. A higher rate of consultation was found among urban IBS subjects than in the rural subjects, with sex not seen to be a discriminator to seek consultation.     

Anxiolytic-like effects of acute and chronic treatment with Achillea millefolium L. extract

Ethnopharmacological relevance

Achillea millefolium L. (Asteraceae), known as yarrow (“mil folhas”), has been used as folk medicine for gastrointestinal disorders, inflammation, anxiety, and insomnia.

Aim

To evaluate the potential anxiolytic-like effect of hydroalcoholic extract of Achillea millefolium L. in animal models.

Methods

The present study evaluated the effects of the hydroalcoholic extract from the aerial parts of Achillea millefolium L. in mice subjected to the elevated plus-maze, marble-burying, and open-field tests. Additionally, the GABA_A/benzodiazepine (BDZ) mediation of the effects of Achillea millefolium was evaluated by pretreatment with the noncompetitive GABA_A receptor antagonist picrotoxin and the BDZ antagonist flumazenil and by [³H]-flunitrazepam binding to the BDZ site on the GABA_A receptor.

Results

Achillea millefolium exerted anxiolytic-like effects in the elevated plus-maze and marble-burying test after acute and chronic (25 days) administration at doses that did not alter locomotor activity. This behavioral profile was similar to diazepam. The effects of Achillea millefolium in the elevated plus-maze were not altered by picrotoxin pretreatment but were partially blocked by flumazenil. Furthermore, Achillea millefolium did not induce any changes in [³H]-flunitrazepam binding.

Conclusion

The results indicate that the orally administered hydroalcoholic extract of Achillea millefolium L. exerted anxiolytic-like effects that likely were not mediated by GABA_A/BDZ neurotransmission and did not present tolerance after short-term, repeated administration.     

Interstitial Lung Disease and Profound Hypoxaemia in a Severely-malnourished Child with Very Severe Pneumonia and Potential Lymph-node Tuberculosis: An Uncommon but Serious Co-morbidity

A nine-month old boy was initially admitted at the Acute Respiratory Infection Unit of Dhaka Hospital of icddr,b and soon after transferred to the Intensive Care Unit of the same hospital. The boy had problems of very severe pneumonia (confirmed by radiology), severe hypoxaemia, severe malnutrition, and Down''s syndrome. The patient was treated according to the hospital protocol for the management of pneumonia and malnutrition. During the hospital stay, hypoxaemia was persistent with very little improvement of pneumonia; a number of differentials, such as pneumocystis jirovecii pneumonia, lymph-node tuberculosis, were added to the problems. Subsequently, the patient''s hypoxaemia improved with the empirical use of antitubercular drugs. However, the patient again developed persistent hypoxaemia and, after unsuccessful treatment for a hospital-acquired pneumonia, the problems further expanded to include interstitial lung disease (ILD). This was confirmed by high-resolution computed tomography, and the patient was treated with prednisolone for 6 months, along with antitubercular drugs. He fully recovered from ILD, hypoxaemia, and pneumonia both clinically and radiologically. Therefore, severely-malnourished children having wet cough and pneumonia with persistent hypoxaemia should be assessed for the possible existence of interstitial lung disease. This may help provide a prompt and appropriate management to reduce morbidity and deaths in such patients.Key words: Hypoxaemia, Infant, Interstitial lung disease, Lymph-node tuberculosis, Severe malnutrition, Very severe pneumonia     

Open-label study of a proprietary treatment program targeting type A gamma-aminobutyric acid receptor dysregulation in methamphetamine dependence

OBJECTIVE: To evaluate the safety and efficacy of the pharmacological component of a proprietary medical treatment program targeting type A gamma-aminobutyric acid receptor dysregulation in adults who met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria for methamphetamine dependence. PARTICIPANTS AND METHODS: A prospective, open-label, single-group study of the medication portion of a proprietary treatment program for methamphetamine dependence was conducted from July 1, 2005, to May 10, 2006, at Research Across America, an outpatient private, for-profit, clinical research company in Dallas, TX. In the study, flumazenil, hydroxyzine, and gabapentin, all of which were approved by the US Food and Drug Administration for indications other than drug dependence, were used off-label for the treatment of methamphetamine dependence. Fifty persons who had used methamphetamine within 7 days of study entry were enrolled and received the treatment. Treatment lasted 4 weeks, followed by 8 weeks of weekly follow-up visits to monitor for methamphetamine use via urine drug tests and self-reporting. RESULTS: Participant retention was higher than expected, with 85% of participants completing the program. Significant decrease in methamphetamine use (P<.001) was noted at 84 days after vs 90 days before treatment. If missing data are counted as days of methamphetamine use, a 47% reduction in use was observed for the entire sample (P<.001) and a 65% reduction for the 36 who completed the 8-week evaluation phase (P<.001). Urine test results and self-reported use were positively correlated (Pearson r=0.72, P<.001). The frequency of cravings was reduced on average by 66% (P<.001), with 30 of 31 (97%) of the 36 who completed the study reporting reduction in cravings. CONCLUSION: Substantial reductions in methamphetamine cravings and use were observed in all phases of treatment, and the retention rate of participants was high. These findings suggest that the efficacy of the medications and of the entire program in treating methamphetamine dependence should be examined in controlled trials.     

Magnesium sulfate and sodium valproate block methylphenidate-induced hyperlocomotion, an animal model of mania

Magnesium sulfate (MgSO4) is used to treat and prevent eclamptic seizures, and several anticonvulsant drugs (e.g., sodium valproate) are clinically effective antimanic drugs. Psychostimulant-induced hyperlocomotion has been proposed as an animal model for the study of antimanic drugs. The present study evaluated the effects of MgSO4 and sodium valproate (as a positive control) on hyperlocomotion induced by methylphenidate in mice. Acute MgSO4 (300-400 mg/kg), but not sodium valproate (100-300 mg/kg), prevented the increase in locomotor activity induced by methylphenidate (5.0 mg/kg). In contrast, repeated treatment (14 days) with valproate (300 mg/kg), but not MgSO4 (400 mg/kg), blocked methylphenidate-induced hyperlocomotion. Thus, acute MgSO4 exerted antimanic-like effects in this animal model.     

The antimanic-like effect of tamoxifen: Behavioural comparison with other PKC-inhibiting and antiestrogenic drugs

Protein kinase C (PKC) is an important cellular target for mood stabilizers such as lithium and valproate, and tamoxifen, an antiestrogenic drug with PKC inhibition activity, also demonstrates an antimanic effect. Thus, the aim of the present study was to evaluate whether the antimanic effect of tamoxifen is mediated through the PKC inhibitory and/or the antiestrogenic action(s) of the drug. In the present study, the effects of tamoxifen, chelerythrine (a PKC inhibitor) and medroxyprogesterone (an antiestrogenic drug) were investigated in amphetamine-induced hyperlocomotion of mice, an animal model of a manic state. Lithium carbonate (100 and 150mg/kg, i.p.), tamoxifen (1.0mg/kg, i.p.) and chelerythrine (1μg/site, i.c.v.) completely blocked the amphetamine-induced hyperlocomotion. However, while the intermediate medroxyprogesterone dose (3.0mg/kg, i.p.) partially reduced the amphetamine-induced hyperlocomotion, lower (1.0mg/g) and higher (6.0mg/kg) doses produced no effect. Our results indicate a major role for PKC inhibition in the antimanic-like effect of tamoxifen, although its antiestrogenic action may also contribute to this effect.     

The effect of bone morphometric changes on orthodontic tooth movement in an osteoporotic animal model

Objective:To elucidate the effect of bone morphometric changes on orthodontic tooth movement (OTM) in zoledronic acid–treated ovariectomized rats.Materials and Methods:Twenty-one 10-week-old female Wistar rats were divided into ovariectomy (OVX), OVX with zoledronic acid administration (OVX + ZOL), and sham operation (control) groups. Two weeks after OVX, ZOL administration was initiated. Twelve weeks after OVX, a nickel-titanium closed-coil spring of 25-g force was applied mesially to the maxillary left first molar. In vivo micro–computed tomography (CT) of the left proximal tibia was performed for bone morphometric analysis every 2 weeks after OVX. In addition, OTM was investigated using micro-CT at 0, 12, and 14 weeks after OVX.Results:There were significant differences in the bone mineral content (BMC), bone volume (BV), BMC to tissue volume ratio (BMC/TV), and BV to TV ratio of trabecular bone between the control and OVX groups and also between the OVX + ZOL and OVX groups. In the OVX + ZOL group, increased BMC and BV in the cortical bone and increased bone mineral density (BMD) in the trabecular bone were observed. Interestingly, OTM in the OVX group was almost two times more than that in the control and OVX + ZOL groups. Moreover, OTM was correlated with BMD, BMC, BV, and BMC/TV in the trabecular bone.Conclusions:OVX accelerated OTM, while ZOL suppressed it. OTM demonstrated a significant negative relationship with trabecular bone mass.     

One-stage cleft repair outcome at age 6- to 18-years -- a comparison to the Eurocleft study data

The optimisation of the relation between quality of outcome and burden of care is difficult in the treatment of cleft lip and palate. We analysed long-term outcome after one-stage repair of clefts to assess the benefits and limitations of this form of treatment. Thirty-three patients aged 6-18 years who had had lip repair, two-flap palatoplasty, and corticocancellous alveolar bone grafts at 6 months of age were divided into three age groups (6-11, 12-14, and 15-18 years) and compared with mean outcome data from the Eurocleft centres and with cephalometric standards of healthy people. Fifteen of the 33 patients were assessed for nasalance. Maxillary protrusion (SNA) and intermaxillary relation (ANB) in the one-stage groups differed significantly from those of healthy people, but not from corresponding means in the Eurocleft study. In 61% the Bergland score for alveolar ossification was grade I or II, and in 15% it was grade III; 24% had secondary alveolar bone grafting. No palatal fistulas occurred and nasalance did not differ significantly from that of healthy controls. As each patient generally had a primary operation and one secondary procedure, they benefited from half the number of surgical steps of multistage procedures. However, one-stage procedures led to significant disturbance in growth, but the degree of this was similar to mean values of multistage procedures in the Eurocleft study. Primary alveolar bone grafting led to inconsistent alveolar ossification and was suspected to interfere with anterior maxillary growth so it has been abandoned.     

Challenges in the management of life-threatening complications caused by a rare case of sarcoid-lymphoma syndrome

International Journal of Colorectal Disease - The sarcoid-lymphoma syndrome is a rare condition where both entities co-exist in the same patient. Overlapping clinical manifestations, imaging...