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Biomedical subjects

D MacKay

Publications and source records attributed to D MacKay.

10 recordsLinked to original sources
PubMed2004

GSK-3beta inhibition reverses axonal transport defects and behavioural phenotypes in Drosophila.

The tauopathies are a group of disorders characterised by aggregation of the microtubule-associated protein tau and include Alzheimer's disease (AD) and the fronto-temporal dementias (FTD). We have used Drosophila to analyse how tau abnormalities cause neurodegeneration. By selectively co-expressing wild-type human tau (0N3R isoform) and a GFP vesicle marker in motorneurons, we examined the consequences of tau overexpression on axonal transport in vivo. The results show that overexpression of tau disrupts axonal transport causing vesicle aggregation and this is associated with loss of locomotor function. All these effects occur without neuron death. Co-expression of constitutively active glycogen-synthase kinase-3beta (GSK-3beta) enhances and two GSK-3beta inhibitors, lithium and AR-A014418, reverse both the axon transport and locomotor phenotypes, suggesting that the pathological effects of tau are phosphorylation dependent. These data show that tau abnormalities significantly disrupt neuronal function, in a phosphorylation-dependent manner, before the classical pathological hallmarks are evident and also suggest that the inhibition of GSK-3beta might have potential therapeutic benefits in tauopathies.

Animals↗
PubMed2001

Hemorrhoids and varicose veins: a review of treatment options.

Hemorrhoids and varicose veins are common conditions seen by general practitioners. Both conditions have several treatment modalities for the physician to choose from. Varicose veins are treated with mechanical compression stockings. There are several over-the-counter topical agents available for hemorrhoids. Conservative therapies for both conditions include diet, lifestyle changes, and hydrotherapy which require a high degree of patient compliance to be effective. When conservative hemorrhoid therapy is ineffective, many physicians may choose other non-surgical modalities: injection sclerotherapy, cryotherapy, manual dilation of the anus, infrared photocoagulation, bipolar diathermy, direct current electrocoagulation, or rubber band ligation. Injection sclerotherapy is the non-surgical treatment for primary varicose veins. Non-surgical modalities require physicians to be specially trained, own specialized equipment, and assume associated risks. If a non-surgical approach fails, the patient is often referred to a surgeon. The costly and uncomfortable nature of treatment options often lead a patient to postpone evaluation until aggressive intervention is necessary. Oral dietary supplementation is an attractive addition to the traditional treatment of hemorrhoids and varicose veins. The loss of vascular integrity is associated with the pathogenesis of both hemorrhoids and varicose veins. Several botanical extracts have been shown to improve microcirculation, capillary flow, and vascular tone, and to strengthen the connective tissue of the perivascular amorphous substrate. Oral supplementation with Aesculus hippocastanum, Ruscus aculeatus, Centella asiatica, Hamamelis virginiana, and bioflavonoids may prevent time-consuming, painful, and expensive complications of varicose veins and hemorrhoids.

Diagnosis, Differential↗
PubMed1999

Stereological estimation of the total number of neurons in the murine hippocampus using the optical disector.

Using a stereological method, the optical disector, we examined three inbred strains of mice (NZB/BINJ, DBA/2, and C57BL/6J) for morphological differences in volume, neuronal number, and density of the pyramidal cell and dentate gyrus granule cell layers of the hippocampus. We found significant differences in volume and neuronal number for both regions between the three strains at 9 weeks of age, but only modest differences in neuronal density. The left dentate volume was 90% larger in the NZB strain and 70% greater in the DBA strain (P<0.0001), and the left pyramidal cell layer was 144% larger in the NZB strain and 150% larger in the DBA strain, than in the B6 strain (P<0.0001). Neuron number in the left dentate was 81% greater in NZB and 37% greater in DBA (P<0.001), and in the left pyramidal cell layer 118% greater in the NZB and 92% greater in the DBA (P<0.01). Differences in neuronal density of the left dentate were not significant (P = 0.060, ns). For the left pyramidal cell layer, neuronal density was 14% greater in B6 and 34% greater in NZB than the DBA strain (P = 0.016). No significant differences were found in left-right laterality, or according to sex. We found that strain accounted for 60% of the variance in hippocampal volume and 44% of neuron number. These differences thus mainly reflect genetic variation in hippocampal volume and may have important implications for brain evolution, behaviour, and human diseases where hippocampal degeneration is involved.

Algorithms↗
PubMed1989

A randomised comparative trial of nicardipine versus amiloride and hydrochlorothiazide in mild to moderate hypertension. A report from the General Practitioner Hypertension Study Group.

In 1984 the General Practitioner Hypertension Study Group undertook a rescreening of their patient population, looking for patients who still had untreated mild to moderate essential hypertension. Suitable patients were entered into a clinical trial comparing the safety and efficacy of nicardipine (a calcium antagonist) and amiloride + hydrochlorothiazide (HCTZ) (moduretic). The study included one year of long-term follow-up. Both drugs significantly lowered BP in both the short and long term. Numbers and percentages of patients from each group reporting adverse experiences were similar in the short term, but in the long term the frequency of adverse event reporting was much lower with nicardipine treatment than with amiloride + HCTZ treatment (2/10 versus 9/17). Treatment with amiloride + HCTZ led to elevations in serum levels of cholesterol, uric acid and urea, which were maintained at one year, whilst no abnormalities in blood biochemistry were seen in patients treated with nicardipine. In conclusion we have found that nicardipine compares very favourably with amiloride + HCTZ in the treatment of mild to moderate hypertensive patients.

Adolescent↗