Experimental Studies of Transplantation and Regeneration of Endocrine Pancreatic Cells

ABSTRACT. Replacement of destroyed B-cells with new "healthy" ones appears to he the most physiological approach to treatment of insulin-dependent (type 1) diabetes. This could be achieved either by transplantation of isolated islets or pancreatic segments or by stimulation of the replicatory activity in the islet cells surviving the acute toxic or infectious insult. The results of our experimental investigations indicate that adult, mature insulin-producing cells can replicate very actively when challenged with a proper stimulus, such as when implanted into obese-hyperglycaemic mice. The growth of transplanted islets is, hawever, dependent on the site of implantation. Thus, the subcapsular space of the kidney is more favourable than the spleen. Furthermore, immunosuppressive therapy may impair islet cell replicatory activity, as demonstrated in this study for Cyclosporin A. In a search for factors stimulating islet cell replication, we found that the hepatotoxic agent galactosamine enhanced this process as observed autoradiographically one week after the injection. This fits in with previous case reports demonstrating increased mitotic activity in islets of patients suffering from various acute liver diseases. Altogether this series of experiments demonstrates that islet cell replication is a more dynamic process than has hitherto been believed. Obviously many conditions influence this process so significantly that an impact on the diabetic state of the patients can well be expected.     

Chronic Pelvic Ischemia: Contribution to the Pathogenesis of Lower Urinary Tract Symptoms (LUTS): A New Target for Pharmacological Treatment?

The incidence of lower urinary tract symptoms, including overactive bladder (OAB), is continuing to rise, and is associated with a negative impact on quality of life and a heavy economic burden. A major risk factor for OAB is advancing age. The etiology of OAB is multifactorial and appears to involve myogenic, neurogenic, and urotheliogenic factors. In this article, we review the strengthening preclinical evidence supporting the contribution of chronic pelvic ischemia to the pathogenesis of OAB. In animal models, chronic ischemia induced by arterial injury and a high‐fat diet upregulates markers of oxidative stress and proinflammatory cytokines in the urothelium and lamina propria, and leads to increased expression of nerve growth factor. These processes result in increased afferent activity and an increased frequency of micturition, reflecting a state of bladder hyperactivity. In severe, prolonged cases, bladder overactivity may develop into underactivity. Antimuscarinic therapies are the mainstay of OAB treatment, but their usefulness is limited by modest efficacy and troublesome side‐effects. Our increasing understanding of the contribution of chronic ischemia to OAB is leading toward novel therapeutic options targeting chronic pelvic ischemia and its morphological, functional, and oxidative consequences. Preclinical trials have demonstrated encouraging results with α₁‐adrenoreceptor blockade, phosphodiesterase type 5 inhibition, β₃‐adrenoreceptor agonism, free radical scavenging, and stem cell therapy, in preventing morphological, biochemical and functional changes induced by chronic bladder ischemia.     

Specialist paediatric dentistry in Sweden 2008 – a 25‐year perspective

International Journal of Paediatric Dentistry 2010; 20: 313–321 Background. Paediatric dentistry in Sweden has been surveyed four times over the past 25 years. During this period postgraduate training, dental health, and the organization of child dental care have changed considerably. Aim. To investigate services provided by specialists in paediatric dentistry in Sweden in 2008, and to compare with data from previous surveys. Design. The same questionnaire was sent to all 30 specialist paediatric dental clinics in Sweden that had been used in previous surveys. Comparisons were made with data from 1983, 1989, 1996 and 2003. Results. Despite an unchanged number of specialists (N = 81 in 2008), the number of referrals had increased by 16% since 2003 and by almost 50% since 1983. There was greater variation in reasons for referrals. The main reason was still dental anxiety/behaviour management problems in combination with dental treatment needs (27%), followed by medical conditions/disability (18%), and high caries activity (15%). The use of different techniques for conscious sedation as well as general anaesthesia had also increased. Conclusions. The referrals to paediatric dentistry continue to increase, leading to a heavy work load for the same number of specialists. Thus, the need for more paediatric dentists remains.     

Expression of HLA-ABC and -DR Locus Antigens on Human Kidney, Endothelial, Tubular and Glomerular Cells

The distribution of the major histocompatibility complex antigens on the various cellular structures of the human kidney was analysed by using a modified Staphalococcus aureus Cowan I method Conventional alloantisera and heterologous antisera raised against Isolated molecules were used for the HLA-ABC antisera were expressed on all types of kidney passenger leucocytes, on vascular endothelial cells, and on kidney tubular cells, but not substantially on the glomerular podocytes, The DR antigens were strongly expressed on (a fraction of) the passenger lymphocytes and on the kidney vascular endothelial cells, weakly on the passenger monocytes, but not measurably on the urine-producing apparatus of the kidney—that is, on the glomerular and tubular cells.     

Pharmacological characterization of postjunctional α-adrenoceptors in isolated feline cerebral and peripheral arteries

The vascular α-adrenoceptors in isolated feline cerebral, lingual and mesenteric arteries were characterized and compared. In the middle cerebral artery the relative order of potency for agonists was: clonidine>oxymetazoline>noradrenaline>phenylephrine which indicates that the postjunctional α-receptor in this vessel is of α₂-type. This view is further supported by the finding that yohimbine, but not prazosin, had a potent, mainly competitive blocking action. In peripheral arteries, clonidine was without effect. In these vessels, the potency difference between phenylephrine and oxymetazoline was more than 40 times less than in cerebral vessels. The pA₂-values for prazosin correlated well with pA₂-values found for the interaction of this drug with α₁-receptors in a variety of other tissues, thus suggesting the occurrence of an α₁-receptor in these arteries. However, the pA₂-values for yohimbine and rauwolscine correlated well with an α₂-receptor, suggesting also the presence of α₂-receptors. Schild plots for prazosin and rauwolscine in lingual arteries displayed slopes significantly lower than unity, which also supports the view of a mixture of α₁-and α₂-receptors in these vessels. However, the Schild plots for the antagonists in mesenteric arteries did not differ significantly from unity, a finding possibly indicating the presence of an α-receptor unable to differentiate between substances that in other tissues act preferentially on α₁- or α₂-receptors.     

Effects of isozyme-selective phosphodiesterase inhibitors on rat aorta and human platelets: smooth muscle tone,platelet aggregation and cAMP levels

The inhibitors of the cGMP-inhibited, low-K_m cAMP phosphodiesterase—milrinone and OPC 3911-and an inhibitor of a non-cGMP-inhibited low-K_m cAMP phosphodiesterase—rolipram—were used to evaluate the functional importance of the two cAMP phosphodiesterase activities in vascular smooth muscle and in platelets. Vinpocetine, an inhibitor of a calcium-calmodulin-dependent phosphodiesterase was also studied. OPC 3911 and milrinone relaxed the contracted rat aorta, inhibited ADP-induced platelet aggregation and also enhanced isoprenaline-induced relaxation as well as the antiaggregatory effects of adenosine. In platelets, OPC 3911 and milrinone increased cAMP levels, but in the rat aorta the increase was significant only for milrinone (OPC 3911 P= 0.062). In both tissues OPC 3911 and milrinone enhanced the increase in cAMP caused by activators of adenylate cyclase (isoprenaline/adenosine). Rolipram had no effects on aggregation or cAMP levels in platelets and no overadditive effects in combination with adenosine. Rolipram had little effect on relaxation and cAMP levels, did not alter isoprenaline-induced relaxation of guanfacin-contracted rat aorta, but showed synergistic effects with isoprenaline in raising cAMP levels. In PGF_2α-contracted aorta rolipram enhanced relaxation caused by isoprenaline. Vinpocetine had a relaxant effect without affecting cAMP levels, but had no effect on platelets. These results support the concept that the cGMP-inhibited phosphodiesterase is an important modulator of vascular smooth muscle tone and platelet function. The role of the non-cGMP-inhibited phosphodiesterase in these tissues is less obvious.     

Cortico-cortical mediation of short-latency (lemniscal) sensory input to the motor cortex in deeply pentobitone anaesthetized cats

In pentobarbitone-anaesthetized cats, responses were recorded as surface positive potentials in the motor cortex on forelimb and brachium conjunctivum stimulation. In such a preparation, the forelimb nerve responses are mediated via the spino-cervical tract and the dorsal column-lemniscal pathway. Lesions of the sensory cortex (sparing only the depth of the coronary sulcus) abolished or reduced short-latency peripheral responses, in the motor cortex, on both skin and muscle nerve stimulation to less than 10% of control, while brachium conjunctivum responses were unchanged. Lesions of the second somatosensory area alone reduced the motor cortex responses on peripheral nerve stimulation by 10–20%. When the sensory cortex were abolished before the spreading depression reached the recording point, as judged from the brachium conjunctivum response. The depth distribution of positive and negative field potentials, constituting the early componentsof a peripheral response in the motor cortex, closely resembled that of a cortico-cortical response evoked on stimulation in area 3. It differed from that of thalamo-cortical response evoked in brachium conjunctivum stimulation. These data suggest that most, if not all, sensory input through the dorsal column and spino-cervical tract to the motor cortex is mediatd via the sensory cortex.