Reduced mitochondrial adenosine triphosphate synthesis in skeletal muscle in patients with Child-Pugh class B and C cirrhosis.

Patients with cirrhosis of the liver often complain of tiredness and a lack of strength at physical exercise. Other investigators have found that muscle strength, work capacity, and maximal oxygen consumption are reduced in cirrhosis. We hypothesized that mitochondrial maximal rate of ATP synthesis in skeletal muscle may be impaired in these patients. This was tested with (31)P nuclear magnetic resonance spectroscopy in anterior tibial muscle of cirrhotic patients and healthy controls at rest, during exercise, and subsequent recovery. In patients with Child-Pugh class B and C cirrhosis resting PCr/P(i) ratio (8.3 +/- 1.0; n = 7) was lower than in patients with Child-Pugh class A cirrhosis (12.1 +/- 2.1; n = 7) and controls (11. 7 +/- 1.1; n = 6; P =.03), while the resting P(i)/gammaATP ratio was higher in Child-Pugh class B and C patients (0.43, 0.30, and 0.27, respectively; P =.03). Maximal rate of mitochondrial adenosine triphosphate (ATP) synthesis (V(max)) as calculated from the initial rate of phosphocreatine (PCr) recovery after work was lower in Child-Pugh class B and C cirrhosis (0.189 mmol/L/s +/- 0.034) than in both Child-Pugh class A patients (0.402 mmol/L/s +/- 0.103) and controls (0.425 mmol/L/s +/- 0.064; P =.01). V(max) was significantly correlated to intracellular free [Mg(2+)] obtained from the (31)P nuclear magnetic resonance (NMR) spectra (P =.003). Insufficient oxygen delivery did not seem a likely cause of reduced ATP synthesis in the patients. These findings suggest either a decreased number of mitochondria in skeletal muscle of the cirrhotic patient in Child-Pugh class B and C or a defective mitochondrial function that could be related to low intracellular free [Mg(2+)].

Effect of capsaicin treatment or inferior alveolar nerve resection on dentine formation and calcitonin gene-related peptide- and substance P-immunoreactive nerve fibres in rat molar pulp.

The aim of this study was to investigate whether decreased sensory innervation induced by capsaicin treatment or axotomy of the inferior alveolar nerve has an effect upon dentine formation in the rat first molar. Dentine formation was visualized by intravital injection of Procion brilliant Red H8BS and denervation was verified immunohistochemically for the neuropeptides calcitonin gene-related peptide (CGRP) and substance P. The observation times were 6 weeks for the capsaicin-treated group and 11 days for the axotomized group. Capsaicin injections caused a consistent reduction in numbers of CGRP- and substance P-immunoreactive fibres in the pulps and a somewhat smaller reduction in the periodontal tissues. Unilateral axotomy of the inferior alveolar nerve induced an almost complete loss of immunoreactive fibres in the pulp and in the mesial gingiva of the first molar. Dentine formation at the mesial pulp horn and at the central pulp floor was significantly reduced in both groups compared to controls. The results suggest that sensory neuropeptides such as CGRP and substance P may play a part in dentine formation.