Coenzyme Q10: clinical benefits with biochemical correlates suggesting a scientific breakthrough in the management of chronic heart failure

There are obviously several causes of myocardial dysfunction but energy deficiency of the myocytes may play a significant role and probably is a common mechanism during the progression of myocardial failure. Theoretically, a poor utilization efficiency of oxygen may be due to exhaustion of the myocardial stores of bioenergetics. In this report the authors review their biochemical results from measurements of coenzyme Q10 (CoQ10) levels in blood and human endomyocardial biopsies using an HPLC method from patients with suspected myocardial disease (n = 45). The levels of CoQ10, which has a key role in the respiratory chain and the synthesis of ATP, was found to be significantly decreased in various groups of patients with myocardial failure (dilated and restrictive cardiomyopathy and alcoholic heart disease) as compared to "normal" myocardium (0.42 +/- 0.04 micrograms/mg dry weight). The deficiency of CoQ10 was more pronounced with increasing symptoms; e.g. patients with dilated cardiomyopathy in NYHA Classes III and IV had lower tissue CoQ10 content than those of Classes I and II (0.28 +/- 0.04 vs. 0.37 +/- 0.06 micrograms/mg, p less than 0.001). Nearly two thirds of a series of 40 patients in severe heart failure (Classes III and IV) treated with CoQ10, 100 mg daily, in an open, controlled design showed subjective and objective improvement. Clinical responders were 69% and 43% of patients with cardiomyopathy and ischaemic heart disease, respectively. The results suggest that CoQ10 is a novel and effective breakthrough in heart-failure therapy and it appears safe, as no adverse reactions were registered. The through in heart-failure therapy and it appears safe, as no adverse reactions were registered.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of short-chain fatty acids on in vitro bacterial growth of Bacteroides fragilis and Escherichia coli

Short-chain fatty acids (SCFA) are produced in the large bowel of nonruminant mammals by bacterial anaerobic fermentation. The aim of the present study was to investigate the effects of SCFA on the in vitro growth of Bacteroides fragilis and Escherichia coli. B. fragilis and E. coli isolated from fresh human clinical samples and a reference strain for each species were incubated in a meat infusion broth with increasing amounts of SCFA and grown under anaerobic conditions at a temperature of 37 degrees C. Bacterial growth was estimated by spectrophotometry. Rate of growth was calculated from the logarithmic growth phase. SCFA, in concentrations normally found in the human colon, had a significant (p<0.01) inhibitory effect of the in vitro growth rate for E. coli, while they were without effect on the in vitro growth rate of B. fragilis. It may be concluded that under in vitro conditions SCFA had growth-inhibitory effects on E. coli, while they had no effect on B. fragilis.     

Differences in contractile properties of anorectal smooth muscle and the effects of calcium channel blockade

BACKGROUND: Pharmacological manipulation of the anal sphincter is hampered by a lack of specificity. This study aimed to determine differences in the role of intracellular and extracellular calcium in the development of tone and agonist-induced contractions between internal anal sphincter (IAS) and rectal circular muscle which might allow targeted manipulation. METHODS: Smooth muscle strips from the IAS and rectal circular muscle of 24 Large White pigs were mounted for isometric tension recording in a superfusion organ bath in the presence of different perfusates. RESULTS: IAS developed tone and spontaneous activity that were abolished by nifedipine, which also reduced contractions to noradrenaline to 72 per cent of control values. Rectal smooth muscle developed spontaneous activity but no tone. Nifedipine abolished the activity and reduced contractions to carbachol to 17 per cent of control. Contractile activity was abolished in both tissues in calcium-free solution. Transient exposure to a high calcium concentration reloaded the stores, and the ability of agonists to release stored calcium was tested after 3 min in calcium-free solution. In IAS, noradrenaline contraction was 76 per cent of control and in rectal circular muscle carbachol contraction was 57 per cent of control. Store loading was prevented by nifedipine in rectal smooth muscle but not IAS. Cyclopiazonic acid reduced store filling in both tissues. CONCLUSION: Agonist-induced contraction of IAS is largely due to release of stored calcium and L-type calcium channels are not needed for store filling. Rectal circular smooth muscle depends more on extracellular calcium and uses L-type calcium channels for agonist-induced contraction and store filling. These differences suggest that targeted manipulation may be possible in patients with anorectal disorders.     

Preoperative radiotherapy for rectal cancer: implications for surgeons, pathologists and radiologists

BACKGROUND: Over 10,000 new cases of rectal cancer are reported in the UK each year and adjuvant treatments, such as preoperative radiotherapy, are now being used almost routinely. METHODS: A literature review was performed on the Medline database for English language publications on preoperative radiotherapy and rectal cancer. The radioresponsiveness of rectal cancer, tumour downstaging, radiological staging of irradiated rectal cancer, effects of radiotherapy on anastomotic integrity, anorectal and genitourinary function, the role of preoperative radiotherapy in local excision of rectal cancer, and the histological changes peculiar to radiotherapy were evaluated. Results and conclusion: Following preoperative radiotherapy, rectal cancer may be downstaged or, occasionally, eradicated histologically. Rectal cancer can now be staged accurately before operation, but this is significantly less reliable following irradiation. The pathological specimen must be examined thoroughly before a tumour can be reported to have been eradicated, especially as unique histological changes are produced by radiotherapy. There is no evidence to suggest that preoperative radiotherapy adversely affects anastomotic integrity. It appears that preoperative radiotherapy has some adverse affects on long-term anorectal dysfunction, but this must not distract from its main objectives in rectal cancer, namely reduced local recurrence rates and improved overall survival.     

Lower Limb Swelling Due to Femoral Aneurysms

A man of 53 presented with left lower limb swelling, which was found to be caused by compression of the femoral vein by a common femoral artery aneurysm. Seven years later a similar situation developed in the opposite limb. On each occasion the diagnosis was confirmed radiologically and the symptoms resolved rapidly following surgery.

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