Efficient production of bioactive insulin from human epidermal keratinocytes and tissue-engineered skin substitutes: implications for treatment of diabetes

Despite many years of research, daily insulin injections remain the gold standard for diabetes treatment. Gene therapy may provide an alternative strategy by imparting the ability to secrete insulin from an ectopic site. The epidermis is a self-renewing tissue that is easily accessible and can provide large numbers of autologous cells to generate insulin-secreting skin substitutes. Here we used a recombinant retrovirus to modify human epidermal keratinocytes with a gene encoding for human proinsulin containing the furin recognition sequences at the A-C and B-C junctions. Keratinocytes were able to process proinsulin and secrete active insulin that promoted glucose uptake. Primary epidermal cells produced higher amounts of insulin than cell lines, suggesting that insulin secretion may depend on the physiological state of the producer cells. Modified cells maintained the ability to stratify into 3-dimensional skin equivalents that expressed insulin at the basal and suprabasal layers. Modifications at the furin recognition sites did not improve proinsulin processing, but a single amino acid substitution in the proinsulin B chain enhanced C-peptide secretion from cultured cells and bioengineered skin substitutes 10- and 28-fold, respectively. These results suggest that gene-modified bioengineered skin may provide an alternative means of insulin delivery for treatment of diabetes.     

Little Leaguer’s shoulder (proximal humeral epiphysiolysis): MRI findings in four boys

Background Shoulder pain is a common problem among adolescent athletes. A possible cause of such pain that can be diagnosed on MRI is a stress injury to the proximal humerus known as Little Leaguer’s shoulder (proximal humeral epiphysiolysis). Objective Our objective was to describe the MRI appearance of Little Leaguer’s shoulder. Materials and methods Four patients (all boys; age range 11–15 years; median 13 years) with clinical, plain radiographic, and MR imaging findings of Little Leaguer’s shoulder were studied retrospectively. Results MRI demonstrated focal physeal widening in all four boys with extension of physeal signal intensity into the metaphysis on T1-weighted and gradient echo coronal and sagittal sequences. T2-weighted sequences were of limited use in demonstrating the physeal widening, which is critical to the diagnosis. Abnormal high T2-signal intensity was seen in the metaphysis adjacent to the focal physeal widening in all the boys. Conclusion Focal extension of normal physeal T1-weighted and gradient echo signal intensity into the adjacent metaphysis is a sign of stress injury in the proximal humeral physis (Little Leaguer’s shoulder). Children should suspend the offending sport to allow healing.     

The BOLD fMRI refractory effect is specific to stimulus attributes: evidence from a visual motion paradigm

Functional magnetic resonance imaging (fMRI) studies have demonstrated that the blood oxygenation level-dependent (BOLD) hemodynamic response (HDR) to a stimulus is reduced by the previous presentation of a similar stimulus. We investigated the dependence of this refractory effect upon stimulus characteristics using a novel adaptation paradigm while scanning subjects using fMRI at 4 T. The stimuli were composed of horizontal stripes that scrolled up, scrolled down, or remained static, randomly presented for 1-s duration with stimulus-onset asynchronies (SOAs) of 2-7 s. We identified regions of interest (ROI) in lateral temporal--occipital cortex that were activated by motion stimuli, regardless of direction or SOA. We found strong evidence for direction specificity in motion-sensitive lateral temporal-occipital (LTO) cortex. For stimuli whose direction of motion reprised that of the previous stimulus (e.g., up preceded by up), the fMRI response was attenuated at short SOAs (2-4 s) compared to long SOAs (5-7 s). However, for stimuli whose direction of motion was opposite that of the previous stimulus (e.g., up preceded by down), little or no refractory effect was observed. Additionally, examination of activity in pericalcarine cortex indicated a similar pattern. We conclude that the fMRI refractory effect predominantly reflects local stimulus-specific neuronal or neurovascular adaptation and is unlikely to be a nonspecific response of large vessels that support broad functional regions.     

Peperomia pellucida in diets modulates hyperglyceamia,oxidative stress and dyslipidemia in diabetic rats

ObjectiveTo investigate the antidiabetic and antioxidant properties of Peperomia pellucida (P. pellucida) in alloxan-induced diabetic rats.MethodsBeside mouse chow, two diets were designed to contain 10%w/w and 20%w/w P. pellucida as supplements respectively. Diabetes was induced in groups of five male albino rats by a single intraperitoneal injection of alloxan. Two groups of diabetic rats and normo rats were each fed one of these diets respectively, while two other groups served as positive and negative controls respectively. A seventh group was fed pelletized mouse chow.ResultsDiabetic rats on diets supplemented with 10%w/w and 20%w/w of P. pellucida for 28 d resulted in reduction of blood glucose level. The level of total serum cholesterol, triglycerides and LDL-cholesterol decreased significantly (P<0.05) with the supplementation diets compared to the untreated diabetic rats. Also treatment with glibenclamide and P. pellucida (10% and 20%w/w) led to increased activities of SOD, CAT and GSH respectively. There was significant (P<0.05) reduction in the level of HDL-cholesterol, Catalase, SOD activities and GSH concentration in diabetic untreated rats. The supplemented diets significantly (P<0.05) reduced lipid peroxidation, which was elevated in untreated diabetic rats. Significant decrease (P<0.05) in the activities of AST, ALT and ALP was also observed in rats fed P. pellucida supplemented diets.ConclusionsThe results from this study indicate that P. pellucida has an antidiabetic and antioxidant properties in experimental diabetes mellitus and thus justifies the acclaimed traditional antidiabetic use.     

Deranged Calcium Signaling in Purkinje Cells and Pathogenesis in Spinocerebellar Ataxia 2 (SCA2) and Other Ataxias

Spinocerebellar ataxias (SCAs) constitute a heterogeneous group of more than 30 autosomal-dominant genetic and neurodegenerative disorders. SCAs are generally characterized by progressive ataxia and cerebellar atrophy. Although all SCA patients present with the phenotypic overlap of cerebellar atrophy and ataxia, 17 different gene loci have so far been implicated as culprits in these SCAs. It is not currently understood how mutations in these 17 proteins lead to the cerebellar atrophy and ataxia. Several pathogenic mechanisms have been studied in SCAs but there is yet to be a promising target for successful treatment of SCAs. Emerging research suggests that a fundamental cellular signaling pathway is disrupted by a majority of these mutated genes, which could explain the characteristic death of Purkinje cells, cerebellar atrophy, and ataxia that occur in many SCAs. We propose that mutations in SCA genes cause disruptions in multiple cellular pathways but the characteristic SCA pathogenesis does not begin until calcium signaling pathways are disrupted in cerebellar Purkinje cells either as a result of an excitotoxic increase or a compensatory suppression of calcium signaling. We argue that disruptions in Purkinje cell calcium signaling lead to initial cerebellar dysfunction and ataxic sympoms and eventually proceed to Purkinje cell death. Here, we discuss a calcium hypothesis of Purkinje cell neurodegeneration in SCAs by primarily focusing on an example of spinocerebellar ataxia 2 (SCA2). We will also present evidence linking deranged calcium signaling to the pathogenesis of other SCAs (SCA1, 3, 5, 6, 14, 15/16) that lead to significant Purkinje cell dysfunction and loss in patients.     

Complex partial seizures simulating schizophrenia

The clinical features that distinguish schizophrenia from the symptomatic psychoses were seen in a patient whose complex partial seizures remained undiagnosed for five years, resulting in 30 psychiatric hospitalizations.     

Asthma: the psychosocial impact among a sample of south western Nigerians

Morbidity and mortality from asthma continues to increase worldwide. Investigations conducted in Western countries have shown that psychiatric morbidity may play a role in increasing mortality due to asthma. However, the association between psychopathology and asthma has not been fully investigated among Nigerian patients. 50 asthmatics seen in the Chest Clinic of the Obafemi Awolowo University Teaching Hospital Complex (OAUTCH), Ile-Ife, were examined using the 30-item general health questionnaire (GHQ-30). A control group of 48 Nigerians with a similar socio-demographic background were also studied. A significantly higher prevalence of psychiatric disorder (50%) were found in the asthmatic group, while only 27.1% of the control group had psychopathology. Twenty-one (87.5%) of the asthmatics with frequent attacks had psychopathology compared to only four (25%) with less frequent attacks. Psychiatric morbidity did not show any relationship to the level of educational attainment or other socio-demographic variables. This result suggests a high prevalence of psychiatric morbidity among Nigerian asthmatics. The management of asthma should take a wholistic approach: physical, as well as the psychosocial factors should be considered.     

The relationship between Rating of Everyday Arm-use in the Community and Home (REACH) scale affected arm-use assessment,activity and participation after stroke

Background and Objectives

While arm function has been traditionally used as a primary goal for upper extremity rehabilitation post-stroke, we propose a simple measure of arm use, which may translate into better activities and participation. The aim was to determine the relationship between arm use and measures of activity and participation.

Methods

This was a cross-sectional study with evaluative components involving community-dwelling individuals with chronic stroke. The Rating of Everyday Arm-Use in the Community and Home (REACH) Scale was used to assess affected arm use, Barthel Index and activity domain of the Stroke Impact Scale (SIS) for activities, and participation domain of the SIS for participation. The participants were also asked if they resumed driving after the stroke.

Results

Forty-nine individuals (mean age = 70.3 ± 11.5 years, male sex = 51%) living with the effects of a stroke for at least 3 months participated in this study. There was a positive relationship between affected arm use and activities (Barthel Index score – r_s = 0.464; SIS activities – r_s = 0.686), participation (r_s = 0.479), and driving (r_s = 0.581). The Barthel Index scores were higher for individuals with dominant arm hemiparesis (p = 0.003) or left hemisphere lesions (p = 0.005). There was also greater arm use in left hemisphere lesions (p = 0.018).

Conclusions

Affected arm use in individuals with chronic stroke is related to activities and participation. Given the importance of arm use in activities and participation after stroke, rehabilitation therapists may consider utilizing the REACH Scale, a simple and quick outcome measure, as a means to assess arm use and implement effective interventions for improving arm use.     

Severe burn trauma from deliberate self-harm: the Sokoto experience

BACKGROUND: Burn injury is one of the most severe forms of trauma that can afflict mankind. Although several forms of suicide and para suicide have been reported worldwide, severe burn injuries from deliberate self-harm have been poorly documented in Africa. AIM: To evaluate the pattern of deliberate self-harm by burning in our environment. METHOD: This is a 5-year retrospective analysis of all patients who sustained burns from deliberate self-harm (DSH) seen at the Usmanu Danfodiyo University Teaching Hospital, Sokoto from June 1998 to May 2003. The patients' data and other necessary information were extracted from the case notes. RESULTS: Seven patients were seen over the study period. There were six females and one male, giving a female to male ratio of 6:1. All the injuries occurred at home from kerosene flame burns. In all cases, the intent was to take the patient's own life. The triggering factors were mainly psychosocio-economic. Six patients had up to secondary education while one patient had a degree certificate. None of the patients was gainfully employed at the time of incidence. Two patients had previously attempted suicide. Only one patient had a history of psychiatric illness. All sustained severe flame burns ranging from 45% - 98% body surface area (BSA). Compliance to treatment was generally poor. All patients were managed at the intensive care unit (ICU) of the hospital.. Five patients died, while the remaining two signed against medical advice (SAMA) during the course of management. The duration of hospital stay ranged from 2 - 10 days. CONCLUSION: Severe burn injury from DSH, although previously poorly documented in Africa, is not uncommon in our environment. The morbidity and mortality are high, not only because of the nature of injury, but probably because of poor compliance to treatment. We advocate community based studies and routine screening of adolescents to identify those at risk. The need for the establishment suicide information, intervention and prevention centre in Nigeria cannot be overemphasised.