Factors regulating condylar cartilage growth under repeated load application.

Mechanical loading can influence the biological behavior of the bone-associated cells leading to adaptive changes in skeletal mass and architecture. SOX9 and PTHrP genes are known to regulate chondrocyte differentiation and delay maturation, ultimately control the endochondral bone formation. To investigate the effects of repeated mechanical loading on bone, 280 Sprague-Dawley rats were used in this experiment. The animals were randomly allocated into experimental and control groups. Repeated mechanical loading was applied through a bite-jumping device in the experimental group. The experimental animals were sacrificed on 10 different time points together with the matched control. Total RNA was extracted from the mandibular condylar cartilage for PTHrP and SOX9 genes quantification using real-time RTPCR. Results showed that PTHrP expression was increased and reached a peak level on the seventh day after mechanical loading was given. Repeated mechanical loading triggered a significant increase of PTHrP expression leading to another peak increment. The expression of SOX9 was highly correlated with the PTHrP expression, and its pattern of expression was similar to that of PTHrP after repeated mechanical loading. In conclusions, repeated mechanical loading on the condyle triggers the expression of PTHrP and SOX9, which in turn promotes condylar cartilage growth.

Growth hormone replacement therapy improves body composition and increases bone metabolism in elderly patients with pituitary disease.

Although a specific GH deficiency (GHD) syndrome in the adult and the response to GH replacement therapy are well recognized, there are few data available on the effect of GH replacement therapy in elderly GH-deficient patients. We studied the effect of GH therapy on body composition and bone mineral density measured by dual energy x-ray absorptiometry, markers for bone metabolism, insulin-like growth factors (IGFs), and IGF-binding proteins (IGFBPs) in 31 patients (6 women and 25 men; aged 60-79 yr; mean, 68 yr) with multiple pituitary hormone deficiencies. The GH response to arginine or insulin was below 3 microg/L (9 mU/L) in all subjects. They were randomized to GH (Humatrope, Eli Lilly & Co.) or placebo for 6 months, followed by 12 months of open treatment. The dose was 0.05 IU/kg x week for 1 month, and after that it was 0.1 IU/kg x week divided into daily sc injections (0.75-1.25 IU/day). There were no changes in any of the measured variables during placebo treatment. GH treatment normalized serum IGF-I in a majority of the patients and increased IGFBP-3 and -5 as well as IGFBP-4 and IGF-II to values within normal range. Lean body mass was increased, and the increase at 6 and 12 months correlated with the increase in IGF-I (r = 0.46; P = 0.010 and r = 0.54, respectively; P = 0.003). GH treatment caused a modest, but highly significant, reduction of total body fat. Mean bone mineral density was not different from that in healthy subjects of the same age and did not change during the observation period. Markers for bone formation (bone-specific alkaline phosphatase activity, osteocalcin, and procollagen I carboxyl-terminal peptide in serum) increased within the normal range, and levels were sustained throughout the study. The bone resorption marker (pyridinoline in urine) was significantly elevated for 12 months. Side-effects were mild, mostly attributed to fluid retention. In two patients with normal glucose tolerance at the start of the study, pathological glucose tolerance occurred in one patient and was impaired in one. In conclusion, elderly patients with GHD respond to replacement therapy in a similar manner as younger subjects, with an improvement in body composition and an increase in markers for bone metabolism. Side-effects are few, and elderly GHD patients can be offered treatment. As long-term risks are unknown, GH doses should be titrated to keep IGF-I within the age-related physiological range.

Quality of life in adults with growth hormone (GH) deficiency: response to treatment with recombinant human GH in a placebo-controlled 21-month trial.

We examined the effect of GH supplementation on the psychological capacity and sense of well-being in 36 patients with adult-onset GH deficiency (GHD). Recombinant human GH was given in a 21-month cross-over, double blind trial, and quality of life was assessed by using three self-rating questionnaires: the Hopkins Symptom Check List (HSCL), the Nottingham Health Profile (NHP), and the Psychological General Well-Being index. In addition, at the final examination the spouses completed a short questionnaire concerning their partner. Before treatment, the patients had lowered quality of life as determined by the HSCL and NHP inventories, and a correlation between the duration of GHD and the reported symptoms was observed. Upon treatment, the HSCL score was lower (better) after placebo administration (mean +/- SD, 84 +/- 21.3) than at baseline (89 +/- 18.9; P = NS) and fell to 80.2 +/- 18.5 (P < 0.001) when active drug was given. The subscales regarding anxiety, fearfulness, and cognition were the most sensitive. It was apparent that the effect determined after GH therapy in part was due to a placebo effect. With NHP, the dimensions of energy and emotions responded most to treatment. Further, the spouses observed their partners to be improved in several aspects of mood and behavior (P < 0.05 to P < 0.0001) when active drug was given. The data thus demonstrate that GH, which is known to have multiple somatic effects, produces an improvement in the quality of life of adults with GHD.

Streptozotocin induced diabetes in minipig: a case report of a possible model for type 1 diabetes?

Studies on the pathogenic process in type 1 diabetes are often performed in animal models. Low-dose administration of streptozotocin has been used to induce diabetes with pathological alterations similar to human type 1 diabetes in the animals. Rodent models are frequently used but there is a need of developing new models including larger animals. In this study we wanted to investigate to what extent a minipig was sensitive to low-dose streptozotocin for induction of diabetes with features of human Type I diabetes. A female Göttingen minipig received two low-doses (40 mg/kg) of streptozotocin with an 11-day interval. Serum was analysed for the presence of the enzyme glutamic acid decarboxylase, isoform 65, (GAD65) and autoantibodies against glutamic acid decarboxylase, isoform 65 (GAD65A), isoform 67 (GAD67A), insulinoma antigen 2 (IA-2) and insulin (IAA). Pancreas tissue was fixated in formaldehyde and was sent for pathoanatomical examination. The minipig became hyperglycaemic after the second injection of streptozotocin. The pathoanatomical examination showed atrophy of the beta-cell population, depletion of insulin with preserved glucagon content. There was no sign of insulitis. Both GAD65 and GAD65A were detected while GAD67A and IAA were absent. It is concluded that chronic diabetes developed after low-dose streptozotocin injection in a female minipig with the characteristics of the end stage of type 1 diabetes. This pilot study suggests that minipigs show promise as a model to induce diabetes by injections of low-dose streptozotocin.

Association between insulin resistance and GAD65-autoantibody levels--a pilot study in an adult non-diabetic population.

The aim of this pilot study was to investigate any association between insulin resistance (IR) and serum levels of autoantibodies against the glutamic acid decarboxylase (GAD65Ab) among adult non-diabetic subjects. Based on calculations of IR using the IR homeostasis model in a Swedish adult non-diabetic population (n = 756) participating in the WHO MONICA-study, an insulin sensitive group (n = 54, M/F:27/27) and an insulin resistant group (n = 46 M/F:24/22) were identified. Serum from the subjects were analysed for the presence of GAD65Ab. There was no significant difference in GAD65Ab levels between the groups. However, there was a correlation between IR and serum GAD65Ab within the insulin sensitive group (Spearman rho 0.4, p < 0.01). Our observation could indicate that IR could serve as an initiator or a progression factor in the autoimmune process in subjects predisposed to autoimmunity. This finding will be further investigated in a larger study including subjects with a continuum of IR.

Root surface caries and periodontal disease in long-term alloxan diabetic rats.

Caries, periodontal disease, and occlusal wear were studied in rats with short-term (one month) and long-term (12 months) untreated alloxan diabetes and in age-matched control rats. Standard laboratory diet and water were given ad libitum. Streptococcus mutans and lactobacilli were naturally occurring inhabitants of the oral bacterial flora. In short-term diabetic rats, there was less dental plaque in the gingival region of the first mandibular molar than in control rats, but the density of leukocytes in the junctional epithelium was increased. Interdentally, the gingival papillae were intact, and the prevalence of foreign material was as low as for the controls. No caries lesions were seen. The proportion of the oral flora which was lactobacilli was positively correlated with the blood glucose level. In long-term diabetic rats, there was more periodontal breakdown than in the age-matched control rats. The periodontal breakdown was always associated with large interdental impactions of foreign material. Caries was seen only in the diabetic rats and in sites with interdental impactions. The decay was shown to start in the cementum at the cemento-enamel junction. The amount of alveolar bone loss, but not the amount of dental caries, was related to the degree of hyperglycemia. Occlusal wear of the molars in long-term diabetic rats was significantly increased as compared with that in the controls.

Soft tissue changes following maxillary osteotomies in cleft lip and palate and non-cleft patients.

A retrospective study of 25 patients with unilateral cleft lip and palate and 25 patients with hypoplastic maxillae without a cleft was carried out to evaluate the effects of maxillary osteotomies at the Le Fort I level on the lip and nose profile. The pre-surgical cephalometric tracing was superimposed twice on the post-surgical cephalogram, on the cranial structures and the anterior maxillary structures, for landmark movement measurement. Results showed statistically significant correlations between soft and hard tissue movement in the cleft group. On average, the ratios of horizontal nasal tip, nasal base and lip movement to underlying hard tissue movement were approximately one fourth, one half and two thirds respectively. The ratio of vertical lip to incisor movement was about one half. The correlations were less significant in the non-cleft group, only the upper lip movement showed statistically significant correlation with hard tissue movement, with a ratio of one half horizontally and one third vertically. It was concluded that in maxillary osteotomy, the cleft group showed a higher soft tissue to hard tissue movement ratio. The correlation between soft and hard tissue movements were more statistically significant in the cleft group than in the non-cleft group. However, though statistically significant, the level of correlation was not strong on an individual basis except in the horizontal lip response of the cleft group. Individual variation was wide and clinical judgement needs to be considered accordingly.

Cutaneous reactions of alloxan diabetic rats to local thermal trauma.

Thermal injury was induced on the external ears of nondiabetic and untreated alloxan diabetic rats of various ages. The skin reaction (erythema and necrosis) was assessed by naked eye inspection, 1, 7, 14 and 21 days after injury. Erythema was found to be more intense in young than in old controls after 1 and 7 days. The late erythematous reaction was more pronounced in short-term diabetic animals than in controls of the same age, indicating that the diabetic metabolic derangement per se alters the reaction. In addition, long-term diabetic rats had a markedly increased skin redness after 1, 7, 14 and 21 days when compared with controls of the same age. Thus, long-term diabetes enhances the erythematous reaction. As to the extent of necrosis, there was no significant differences between the experimental groups. There was, however, a tendency for an increased amount in the long-term when compared with the short-term diabetic rats.

Discrepancies between CT and EEG findings after acute cerebrovascular disease.

Combined EEG and brain CT examinations were performed in 33 patients during the 1st and 2nd week after stroke. CT was abnormal in 17 patients (51%) and EEG was abnormal in 24 patients (72%). In 17 patients CT and EEG showed conflicting results; in 5 patients with normal EEG findings CT was pathological, and 12 patients had normal CT but pathological EEG findings. In this latter group, there were 5 particularly interesting cases with normal CT and a prominent unilateral EEG abnormality. Recently patients with this combination of findings have been described where further investigations disclosed internal carotid occlusion, which could be treated surgically. It is suggested that EEG should be more extensively used when CT findings are negative after stroke, and if a major unilateral EEG abnormality is encountered in such cases, further investigations with angiography should be considered in order to exclude surgically treatable internal carotid occlusion.

Malignant diabetes mellitus--a case report.

A 30-year-old man presented at the diagnosis of an insulin dependent diabetes mellitus with pronounced and multiple complications, such as retino-, nephro-, dermo- and neuropathy. His diabetes had a malignant course and he died from uremia within one year after diagnosis. There were no signs of atherosclerosis at autopsy but in several organs there were pronounced diabetic small vessel lesions.

Local traumatization with heat--cutaneous reactions and early effects on serum zinc concentration in rats with alloxan diabetes of very short duration.

Local heat trauma was induced in rats with alloxan diabetes of 3 days' duration. The cutaneous reaction, water content of the skin and serum zinc concentration were estimated. Petechiae within the area of traumatization were observed more often and were more abundant in the controls than in the diabetic animals. There was no difference between diabetic animals and controls with regard to the increase of water content of traumatized skin or to the water content of non-traumatized skin. There was no difference in serum zinc levels between non-traumatized diabetic animals and controls. After traumatization there was a decrease of serum zinc levels in both animal groups, but to a significantly lower level in the diabetic animals compared to the controls.

Early cutaneous reactions to local traumatization with heat in alloxan diabetic rats.

The effect of cutaneous traumatization with heat in connection with intravenous injection of Evans blue was studied in short-term alloxan diabetic rats. The effect of traumatization was dependent on the degree of traumatization. There was no difference between diabetic animals and controls. The water content of traumatized and non-traumatized skin was determined. There was no difference between diabetic animals and controls with regard to the increase in water content of traumatized skin. Histological and histochemical studies on the effect of surgical cutaneous traumatization did not reveal any differences between diabetic and non-diabetic animals. The results are compared with earlier observations in alloxan diabetic animals with and without ketosis and in long-term diabetes.

Magnesium therapy in type 1 diabetes. A double blind study concerning the effects on kidney function and serum lipid levels.

To test the hypothesis that magnesium depletion might be of importance for the development of vascular complications in diabetes mellitus we performed a randomized, double-blind, placebo-controlled study during 12 months with 20-30 mmol/day of oral magnesium hydroxide in 28 type 1 diabetic patients. Urinary albumin excretion, Cr-EDTA-clearance and certain blood cardiovascular risk factors were measured. At the end of the study there were no significant differences of these parameters between the two groups, except that serum triglyceride values increased in three magnesium treated patients who either showed an increase in blood glycosylated hemoglobin values or body weight during the study.

Prediction of caries in 1 1/2-year-old children.

The aim was to test the predictive ability of defined levels of dietary and oral hygiene habits and also mutans streptococci and lactobacilli in saliva, separately and in combinations, in 1 1/2-year-old children. The population consisted of 181 children, who were investigated with respect to the above factors together with general health, use of fluoride in tablets and/or toothpaste, gingival condition and caries prevalence. Initially, 99% of the subjects were caries-free as against 72% at the age of 3 years, with a mean of 0.8 ds. Using data for sensitivity and specificity the predictive values for positive (PV+) and negative (PV-) tests were calculated for different levels and combinations of variables. A dividing line between high and low caries risk that combined high sensitivity and high specificity could not be established for any variable or combination of variables. High sensitivity was noted with diet as the predictor, high specificity with oral hygiene or occurrence of mutans streptococci. Lactobacilli were excluded as they were found in only 6 children. A two-step computation with mutans streptococci as second predictor improved the ability to single out children with caries at the age of 3 years. Subgrouping and analyses of the material as regards use of fluoride did not influence the results. To sum up, prediction at the age of 1 1/2 years, in a population with a low caries prevalence, was not successful with the variables used in this study.