Effects of enkephalins and two enzyme resistant analogues on monoamine synthesis and metabolism in rat brain

Summary Methionine-enkephalin and leucineenkephalin, administered into the lateral ventricle of intact rats, increased the accumulation of DOPA by a naloxone-sensitive mechanism in different brain regions after inhibition of the aromatic l-amino acid decarboxylase. Because of the rapid enzymatic degradation of both enkephalins large doses (500 g) were required to enhance brain catecholamine synthesis. The two enzyme resistant enkephalin analogues d-Ala²-methionine enkephalin amide (DALA (4–256 g) and FK 33-824 (0.003–1 g) also increased the synthesis of DOPA, dose-dependently and by naloxone-sensitive mechanisms, but at much lower dosage level. The enkephalins markedly enhanced the brain tyrosine concentration but this effect was not antagonized by naloxone, probably because the enzymatic cleavage releases tyrosine from the administered peptides. In contrast, neither DALA nor FK 33-824 increased the brain tyrosine concentration. The formation of 5-HTP and the brain tryptophan concentration were also increased by the enkephalins, although these effects were not blocked by naloxone. The enkephalin analogues, however, enhanced the formation of 5-HTP and the brain tryptophan concentration by naloxonesensitive mechanisms. All four peptides accelerated the disappearance of dopamine, noradrenaline and 5-hydroxytryptamine after inhibition of monoamine synthesis. The results suggest that endogenous enkephalins, through the activation of opiate receptors, are involved in the short-term regulation of central monoaminergic systems.Preliminary data were presented at the Nobel Symposium 42, Principles for the Central Regulation of the Endocrine System, Stockholm, June 8–10, 1978, and at the 4th International Catecholamine Symposium, Asilomar Conference Center, Pacific Grove, California, September 17–22, 1978     

The adjuvant effect of tuberculin in experimental sensitization to merthiolate

Summary When guinea pigs were sensitized to tuberculin by exposure to complete Freund's adjuvant the size of the intradermal PPD test was positively correlated to the body weigth of the animal. Old Tuberculin showed stimulating effect in a subsequent sensitization to merthiolate (thimerosal). The high frequency of delayed cutaneous allergy to merthiolate in the Swedish population is probably explained by sensitization through intradermal testing with tuberculin containing merthiolatc as a preservative.

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Zusammenfassung Bei Meerschweinen, die mit Hilfe von Freunds Adjuvant gegen Tuberculin sensibilisiert wurden, konnte eine Korrelation zwischen der Größe des Intracutantests und dem Körpergewicht der Tiere festgestellt werden. Old Tuberculin zeigte in einem darauffolgenden Sensibilisierungsversuch mit Merthiolat einen stimulierenden Effekt auf die allergische Reaktion gegen Merthiolat. Die hohe Frequenz von allergischen cutanen Spätreaktionen gegen Merthiolat in der schwedischen Bevölkerung ist wahrscheinlich als Sensibilisierung durch Intracutantest mit Tuberculin, das als Konservierungsmittel Merthiolat enthält, zu erklären.

     

The use of non-invasive probes and (13)C nuclear magnetic resonance spectroscopy to assess liver metabolism in humans

Two new methods to assess liver metabolism in humans will be discussed, non-invasive probes and (13)C NMR (nuclear magnetic resonance) spectroscopy. Hepatic UDP-glucose and alpha-ketoglutarate can be sampled by non-invasive probes. This method has been used to quantitate the contribution of the indirect pathway to liver glycogen formation and to estimate relative flow rates and carbon exchange in the Krebs cycle. (13)C NMR spectroscopy has been developed to measure liver glycogen concentrations in vivo. Using this method in combination with measurements of whole body glucose production during fasting, the contribution of gluconeogenesis has been calculated.     

Evaluation of micromotion in cemented vs uncemented knee arthroplasty in osteoarthrosis and rheumatoid arthritis. Randomized study using roentgen stereophotogrammetric analysis

Twenty-four patients (25 knees) with osteoarthrosis (OA) and 19 patients (20 knees) with rheumatoid arthritis (RA) were operated with bi-tricompartmental knee arthroplasty. The patients were randomized to cemented or cementless fixation of the tibial component. The fixation of the tibial components was examined with roentgen stereophotogrammetric analysis (RSA) up to 24 months after operation. The following parameters representing tibial component micromotion were measured: (1) maximum migration of the prosthetic edge (maximum total point motion, MTPM); (2) distal migration of the prosthetic center (subsidence); (3) maximum proximal movements of the prosthetic edge ("lift-off"); and (4) prosthetic rotations, corresponding to internal/external rotation, adduction/abduction, and forward/backward tilt of the tibial component. All prostheses displayed significant micromotions, which tended to decrease 3-6 months after the operation. The average migration after 2 years, when measured as maximum single axis rotation, and MTPM were about 0.9 degrees-1.5 degrees and 1.0-1.5 mm, respectively, in all four groups. There were no statistically significant differences between cemented and cementless prostheses in either the OA or the RA group. The fixation in the RA patients did not significantly differ from that of the OA patients, perhaps because the RA patients had lower weight and were living a more sedentary life.     

A prospective study of body size in different periods of life and risk of premenopausal breast cancer.

The prevalence of obesity at all ages is increasing epidemically worldwide. Information on the association between premenopausal breast cancer and body size during childhood and teenage years is scarce. In 1991 to 1992, a prospective cohort study was assembled in Norway and Sweden. We included in the analysis presented here 99,717 premenopausal women. During the follow-up period, which ended in December 1999, 733 of these women developed a primary invasive breast cancer. Overweight and obesity [body mass index (BMI) > 25 kg/m(2)] at enrollment was associated with a decreased risk of premenopausal breast cancer (P for linear trend = 0.007). Apparent associations between perceived body shape at age 7 and BMI at age 18, with heavier builds at both ages seemingly being protective for premenopausal breast cancer risk, lost their statistical significance after adjustment for BMI at cohort enrollment. Body size at age 7 was correlated with BMI at age 18 (r = 0.43); BMI at age 18 was correlated with adult BMI (r = 0.48). Changes in body size from age 7 or 18 to adulthood did not affect per se risk of premenopausal breast cancer risk. Height was related to risk, with a statistically significantly 30% reduced risk only in women shorter than 160 cm as compared with taller ones. The decreased risk of premenopausal breast cancer was observed in overweight and obese women without, but not in those with, a family history of breast cancer.     

The Swedish Snus and the Sudanese Toombak: are they different?

In Sweden, snuff (locally known as snus), was introduced since the year 1637. Presently, Sweden has the highest per capita consumption and sale figures of snuff in the world, and the habit is becoming increasingly popular. Snus is manufactured into a dry form used in the nasal cavity and a moist form used in the oral cavity. Snus manufactured for oral use is a moist ground tobacco of Dark Kentucky or Virginia species mixed with an aqueous solution of water and other blending ingredients. This form of snuff is found in two types: (1) loose and (2) portion-bag-packed. These are the most widely used. The loose moist form (1–2 g a quid) is the most popular type consumed by 73% of the males, followed by the portion-bag-packed form (0.5–1 g a quid), consumed by 13% of the males, while 14% of the males are mixed users. The majority of snus users place the quid in the vestibular area of the upper lip, and the prevalence among persons 15 years of age or older is 15.9% among males and 0.2% among females. The pH of snus has declined from a previous range of 8–9 to a range of 7.8–8.5, moisture content ranges 35–60% and nicotine content is in the order of 5–11 mg/g dry wt tobacco-specific N-nitrosamines (TSNAs) in micrograms (N′-nitrosonornicotine: NNN 5–9; 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone: NNK 1–2; N′-nitrosoanatabine: NAT 2–5). In the Sudan, snuff, locally known as toombak, was introduced approximately 400 years ago. It is always processed into a loose moist form, and its use is widespread in the country. Tobacco used for manufacture of toombak is of the species Nicotiana rustica, and the fermented ground powder is mixed with an aqueous solution of sodium bicarbonate. The resultant product is moist, with a strong aroma, highly addictive and its use is widespread particularly among males. Its pH range is 8–11, moisture content ranges 6–60% and nicotine content is from 8 to 102 mg/g dry wt, and TSNAs contents in micrograms (NNN 420–1 550; NNK 620–7 870; NAT 20–290). Snus and toombak dippers develop a clinically and histologically characteristic lesion at the site of dipping. Probably due to control of the TSNAs in snus, this type of snuff is associated with a lower risk of cancer of the oral cavity (relative risk: RR 5–6-fold), whereas the risk for cancer of the oral cavity among toombak users was high (RR 7.3–73.0-fold). In conclusion, the two snuff products significantly differ in many aspects. Most notable differences are tobacco species, fermentation and ageing, nicotine and TSNAs content, pH, expression of the p53 tumour supressor gene, and keratin types 13, 14, and 19. It was, therefore, the object of the present study to highlight the oral health hazards of toombak, and to compare it with snus regarding the aforementioned differences.     

Passive tensile stress and energy of the human hamstring muscles in vivo

The present study measured passive resistance to stretch in the hamstring muscles during a standardized stretch maneuver to estimate tensile forces and energy of the individual hamstring muscles in 7 flexible and 6 inflexible persons defined according to joint range of motion. Using a dynamometer, knee joint moment was measured during slow passive knee extension to a maximal angle (dynamic phase) followed by a 90-s static phase. Cross-sectional areas (CSA) of the separate hamstring muscles were obtained with magnetic resonance (MR) imaging. Mathematical modeling was used to calculate instantaneous muscle length and joint moment arm for each muscle. Subsequently, passive muscle tension (N/cm2) was calculated based on moment arm lengths, knee joint moments, and CSA. Maximal tolerated joint angle was greater in flexible (delta1.30+/-0.06 rad) than inflexible (delta0.84+/-0.06 rad) subjects, P<0.01. The peak tension at maximal angle was greater in flexible (81.8+/-12.5 N/cm2) than inflexible subjects (29.3+/-4.1 N/ cm2), P<0.001. For the separate muscles the overall change in muscle length (delta cm) and moment arm (delta cm) differed between groups, P<0.01. Similarly, muscle stiffness (delta tension/delta muscle length) was greater in flexible than inflexible subjects in the final 3 cm, P<0.01, and in the final 20% of length change, P<0.01. Absorbed energy (mJ/cm2) was greater in flexible than inflexible subjects in the final 40% of length change, P<0.05. These data show that flexible persons can attain a greater angle of stretch with an accompanying greater tensile stress and energy than inflexible persons due to an apparent greater tolerance to the externally applied load, and larger change in moment arm. The obtained stress data appear to be in the toe region of a 'classical' stress-strain curve, and energy rather than stiffness may therefore be more appropriate to analyze during the stretch procedure.     

Can the hamstring muscles protect the anterior cruciate ligament during a side‐cutting maneuver?

Because anterior cruciate ligament (ACL) injuries are common in European handball the present study assessed knee joint shear forces to estimate ACL loading in six elite female handball players during a side-cutting maneuver. A pilot investigation in three dimensions showed that peak moments occurred in the sagittal plane at a high velocity. Therefore, analysis of the movement was performed in two dimensions using high-speed cinematography, ground reaction forces, and electromyography (EMG). Film and force plate data allowed for calculation of net joint moments (inverse dynamics), estimates of instantaneous muscle-tendon lengths, contraction velocities, and peak loading of the ACL. During the breaking phase of the maneuver the peak knee joint moment was 239 Nm (99-309), which yielded an ACL-load of 520 N (215-673). The corresponding peak EMG amplitudes for the hamstring muscles were 34-39% of maximum EMG. During the breaking phase the quadriceps muscle contracted eccentrically with a velocity of 216-253% fiber length/s. In contrast, the hamstring muscles contracted concentrically with a velocity of 222-427% fiber length/s. These results suggest that a side-cutting maneuver produces loads that are insufficient to rupture the ACL. Furthermore, the rapid concentric hamstring contraction suggests that even during maximal activation, the ability of the hamstrings to reduce the ACL load is marginal.     

Detection and characterisation of renal lesions by multiphasic helical CT

Purpose: The fast helical CT technique allows examination of the kidneys during different phases of contrast medium enhancement. However, every additional phase increases the radiation dosage to the patients. We investigated the detection rate and characterisation of renal lesions during different phases and evaluated them separately, and considered the possibility of excluding phases without loss of important information.Material and Methods: Sixty patients who underwent contrast-enhanced multiphasic renal helical CT examination were included. Every CT phase was evaluated separately. The number of lesions and the characteristics of the lesions were noted and all lesions were viewed together.Results: A total of 153 cysts and 17 solid lesions were detected. The largest and an equal number of cysts (142/143) was detected in the nephrographic and excretory phases. However, the nephrographic phase detected more cortical cysts and the excretory phase detected more sinus cysts. All solid lesions were detected in all phases. Renal parenchymal tumours were best characterised in the cortical phase and angiomyolipomas in the native phase.Conclusion: The cortical phase was best for characterisation of renal parenchymal tumours. The nephrographic and excretory phases were best in detecting and characterising renal cysts. The nephrographic phase was the phase giving the least diagnostic information.     

CGMP increases in satellite cells of nitric oxide synthase-containing sensory ganglia

cGMP and the enzymes, nitric oxide synthase (NOS) and heme oxygenase-1 (HO-1), the products of which stimulate soluble guanylyl cyclase activity, were investigated in cultured dorsal root ganglia (DRG), and nodose ganglia of adult rats. A dramatic increase of cGMP-positive satellite cells in ganglia cultured for 24 or 48 h was observed, particularly in Th8-L2 DRG and in nodose ganglia. These ganglia also contained most NOS-positive neurones, as reflected by NADPH-diaphorase histochemistry. HO-1 immunoreactivity increased in satellite cells, but in different cells to those in which cGMP increased. These results suggest that both NO and CO could be involved in signalling between neurones and satellite cells in sensory ganglia during regeneration.