Studies on the absorption of elemental diets containing "small peptides" as a nitrogen source

Previous studies have shown that small peptides (di-or tri-peptide) are more rapidly and more evenly absorbed through the small intestine than free amino acid mixture of the same amino acid composition. Since a method to produce protein hydrolysate rich in di-or tri-peptide (SP) was developed, absorption studies were performed to ascertain if the SP shows superior efficiency in absorption to the free amino acid mixture (AA) and large peptide (LP) of the same amino acid composition. A practical elemental diet which contained SP as a nitrogen source, was made (SP-ED) and the absorption rates of nitrogen, carbohydrate and water were studied using dog Thiry-Vella loop in comparison with ED prepared with AA (AA-ED) or LP (LP-ED) with the same amino acid composition. The results are as follows: 1) Absorption rates of nitrogen and water in SP were higher than in AA and LP, when the osmolarities of these solutions were not adjusted to the same level. 2) When the osmolarities of the solutions were adjusted to the same level using mannitol, the absorption rate of nitrogen was still the highest in SP. 3) Nitrogen absorption rate was significantly higher in SP-ED than in AA-ED and LP-ED and carbohydrates were absorbed to a significantly greater extent from the SP-ED than from the AA-ED. These results indicate that small peptides are suitable for use as the nitrogen source for ED.     

Validity and reliability of the Japanese version of the Neuropsychiatric Inventory Caregiver Distress Scale (NPI D) and the Neuropsychiatric Inventory Brief Questionnaire Form (NPI-Q)]

OBJECTIVE: Neuropsychiatric disturbances are common and burdensome symptoms of dementia. Assessment and measurement of neuropsychiatric disturbances are indispensable to the management of patients with dementia. Neuropsychiatric Inventory (NPI) is a comprehensive assessment tool that evaluates psychiatric symptoms in dementia. We translated the NPI-Caregiver Distress Scale part of NPI (NPI-D) and NPI-Brief Questionnaire Form (NPI-Q) into Japanese and examined their validity and reliability. SUBJECTS AND METHODS: The subjects were 152 demented patients and the caregivers who lived with them. These patients consisted of 76 women and 76 men; their mean age was 73.9 +/- 7.8 (S.D.; range: 49 to 93) years. Their caregivers consisted of 46 men and 106 women; their mean age was 65.0 +/- 11.4 (S.D.; range: 35 to 90) years. The Mini-Mental State Examination (MMSE) was conducted with all patients and NPI-Q, NPI, NPI-D, and the Zarit caregiver burden interview (ZBI) were conducted with all caregivers. We examined validity of NPI-D by comparing its score with the MMSE and ZBI scores, and the validity of NPI-Q by comparing its score with the NPI and NPI-D scores. In order to evaluate test-retest reliability, NPI-D was re-adopted to 30 randomly selected caregivers by a different examiner one month later and NPI-Q was re-executed by 27 randomly selected caregivers one day later. RESULTS: Total NPI-D score was significantly correlated with ZBI (rs = 0.59, p < 0.01). Test-retest reliability of NPI-D was adequate (ri = 0.47, p < 0.01). Total NPI-Q severity score and distress score were strongly correlated with NPI (r = 0.77, p < 0.01) and NPI-D (r = 0.80, p < 0.01) scores, respectively. Test-retest reliability of the scores of NPI-Q was acceptably high (the severity score; ri = 0.81, p < 0.01, the distress score; ri = 0.80, p < 0.01). CONCLUSION: The Japanese version of NPI-D and NPI-Q demonstrated sufficient validity and reliability as well as the original version of them. These are useful tools for evaluating psychiatric symptoms in demented patients and their caregivers' distress attributable to these symptoms.     

Temporal and spatial expression of transforming growth factor-β in the healing patellar ligament of the rat

We investigated the temporal and spatial expression of transforming growth factor-β in the healing patellar ligament of the rat by immunohistochemistry. The mid-portion of the medial half of the patellar ligament in 14-week-old male Wistar rats was cut transversely with a scalpel. On day 1 after ligament injury, diffuse staining for transforming growth factor-β was observed in the extracellular matrix filling the wound, and the staining in the adjacent ligament tissue was as weak as it was in the normal ligament. On day 3, the intensity of the diffuse extracellular staining decreased, and the staining was observed in correspondence with the cellular distribution in the wound site and in the adjacent uninjured ligament tissue. On day 7, the intense staining was widely distributed over the whole length of the ligament tissue. On day 28, the staining for transforming growth factor-β was still observed at the wound site and in the adjacent uninjured ligament tissue, where the staining was reduced in intensity but still stronger than it was in the normal ligament. On day 56, the expression of transforming growth factor-β was still detectable at the wound site: however, in the adjacent uninjured ligament tissue, it had almost subsided to the normal level. The results of the present study suggest that ligament healing may be accompanied by extensive changes in the expression of transforming growth factor-β over the whole length of ligament tissue.     

Excursion of the flexor digitorum profundus tendon: a kinematic study of the human and canine digits

The most common problem following primary flexor tendon repair is the failure of the tendon apparatus to glide, secondary to the formation of adhesions. Early motion following tendon repair has been shown to be effective in reducing adhesions between the tendon and the surrounding sheath. Therefore, it is important to determine the amount of flexor tendon excursion along the digit during joint motion. In this study, the excursion between the flexor digitorum profundus (FDP) tendon and the sheath was examined in both human and canine digits. Based on roentgenographic measurements and joint kinematic analysis, the motion of the bones, the FDP tendon, and the sheath were measured with respect to joint rotations. It was found that the canine flexor tendon apparatus behaved similarly to that of the human for the motions studied. The amount of tendon excursion was very small in regions distal to the joint in motion (approximately 0.1 mm/10 degrees of joint rotation). There was little displacement of the sheath (0.2-0.3 mm), except at the metacarpal joint region during metacarpophalangeal (MCP) joint motion and at the proximal interphalangeal (PIP) joint region during PIP joint motion. Tendon excursion relative to the tendon sheath was the largest in zone II during PIP joint rotation (1.7 mm/10 degrees of joint rotation). These results suggest that PIP joint motion may be most effective in reducing adhesions following tendon repair in zone II.     

Rhythmical contractions in pulmonary arteries of monocrotaline-induced pulmonary hypertensive rats

Rhythmical contractions accompanied by an increase in cytosolic Ca2+ concentrations were produced in ring preparations of endothelium-denuded pulmonary arteries from monocrotaline-treated rats, but not in those from vehicle-treated rats, 2-3 h after a resting tension of 15 mN (150-180% of the initial wall length of the artery) was applied. The rhythmical contractions were abolished by nicardipine and ryanodine. Cyclopiazonic acid reduced the relaxation phase of the rhythmical contractions, finally leading to a sustained contraction. Similarly, apamin caused a sustained contraction, whereas charybdotoxin increased the amplitude of the rhythmical contractions. Glibenclamide had no apparent effects on them. Indomethacin and the prostaglandin H2/thromboxane A2 receptor antagonist SQ29548 abolished the rhythmical contractions and reduced the tension, but the thromboxane synthase inhibitor ozagrel had no effect. These results suggest that optimal stretch induces rhythmical contractions in the pulmonary arteries of monocrotaline-induced pulmonary hypertensive rats, to which both Ca2+ influx through voltage-operated Ca2+ channels and Ca2+ release from the endoplasmic reticulum seem to contribute. It is also suggested that small-conductance Ca(2+)-activated K+ channels participate in the relaxation phase of rhythmical contractions. Furthermore, prostaglandin H2 released from nonendothelial cells is likely to play a pivotal role in the induction of rhythmical contractions.     

Serum cholesterol levels as a risk factor of cardiovascular disease

By summing up a series of epidemiological evidence a continuous elevation of total serum cholesterol, especially LDL-cholesterol, leads atherosclerosis and causes the narrowing or occlusion of coronary artery which introduces acute myocardial infarction or angina pectoris in the heart. In the brain, it is a risk factor for cerebral thrombosis. On the other hand, a lower level, 160 mg/dl or less of total serum cholesterol relates with the higher incidence of cerebral hemorrhage or subarachnoid hemorrhage, but still with the lower incidence of ischemic heart disease. It is concluded that the higher the total serum cholesterol level and the longer the period of continuous elevation is, the higher the incidence of ischemic heart disease. And there is a U-shape relationship between the level of serum cholesterol and cerebrovascular disease as a whole with a nadir around 160 to 200 mg/dl which means an optimal range of total serum cholesterol. A subject with total serum cholesterol over the optimal level may need some sort of modification in his daily life, in eating or physical exercise but not necessarily requires any pharmacological therapy.     

Short half-lives of ataxia-associated aprataxin proteins in neuronal cells

Early-onset ataxia with ocular motor apraxia and hypoalbuminemia (EAOH)/ataxia with oculomotor apraxia type 1 (AOA1) is caused by mutations in the gene encoding aprataxin (APTX). Although several in vitro findings proposed that impaired enzymatic activities of APTX are responsible for EAOH/AOA1, potential instability of mutant proteins has also been suggested as the pathogenesis based on in vivo finding that mutant proteins are almost undetectable in EAOH/AOA1 tissues or cells. The present study aimed to experimentally prove instability of mutant proteins in neuronal cells, the cell type preferentially affected by this disease. Results of pulse-chase experiments demonstrated that all of the disease-associated mutants had extremely shorter half-lives than the WT. We further found that mutants were targeted for rapid proteasome-mediated degradation. These results help establish pathogenic and physiological protein characteristics of APTX in neuronal cells.