Frondoside A enhances the antiproliferative effects of gemcitabine in pancreatic cancer.

Pancreatic cancer has a very poor prognosis. While gemcitabine is the mainstay of therapy and improves quality of life, it has little impact on survival. More effective treatments are desperately needed for this disease. Frondoside A is a triterpenoid glycoside isolated from the Atlantic sea cucumber, Cucumaria frondosa. Frondoside A potently inhibits pancreatic cancer cell growth and induces apoptosis in vitro and in vivo. The aim of the present study was to investigate whether frondoside A could enhance the anti-cancer effects of gemcitabine. Effects of frondoside A and gemcitabine alone and in combination on proliferation were investigated in two human pancreatic cancer cell lines, AsPC-1 and S2013. To investigate possible synergistic effects, combinations of low concentrations of the two drugs were used for a 72 h treatment period in vitro. Growth inhibition was significantly greater with the drug combinations than their additive effects. Combinations of frondoside A and gemcitabine were tested in vivo using the athymic mouse model. Xenografts of AsPC-1 and S2013 cells were allowed to form tumours prior to treatment with the drugs alone or in combination for 30 days. Tumours grew rapidly in placebo-treated animals. Tumour growth was significantly reduced in all treatment groups. At the lowest dose tested, gemcitabine (4 mg/kg/dose), combined with frondoside A (100 µg/kg/day) was significantly more effective than with either drug alone. To conclude: The present data suggest that combinations of frondoside A and gemcitabine may provide clinical benefit for patients with pancreatic cancer.

Targeted disruption of the galectin-3 gene results in decreased susceptibility to multiple low dose streptozotocin-induced diabetes in mice.

Galectin 3 (Gal-3) is an antiapoptotic and a proinflammatory lectin. We hypothesized that the proinflammatory properties of Gal-3 may influence disease induction in the multiple low doses of streptozotocin model of diabetes. Diabetes was induced in C57BL/6 Gal-3(+/+) and Gal-3(-/-) mice and disease monitored by blood glucose level, immuno-histology, insulin content of islets and expression of the proinflammatory cytokines, TNF-alpha, IFN-gamma, IL-17, and iNOS in pancreatic lymph nodes. Gal-3(+/+) mice developed delayed and sustained hyperglycemia, mononuclear cellular infiltration and reduced insulin content of islets accompanied with expression of proinflammatory cytokines. Gal-3(-)/(-) mice were relatively resistant to diabetogenesis as evaluated by glycemia, quantitative histology and insulin content. Further, we observed the weaker expression of IFN-gamma and complete absence of TNF-alpha, and IL-17 in draining pancreatic lymph nodes. Macrophages, the first cells that infiltrate the islet in this model of diabetes, produce less TNF-alpha and NO in Gal-3(-/-) mice. Thus, Gal-3 is involved in immune mediated beta cell damage and is required for diabetogenesis in this model of disease.

Long-term changes in sympathetic innervation in the corpus cavernosum of the STZ-diabetic rat.

The noradrenaline (NA) concentration in the rat corpus cavernosum (CC) increased to approximately 350% of control values after about 8 weeks of hyperglycaemia induced by the intraperitoneal injection of streptozotocin (STZ) at 10 weeks of age. These changes were maintained for at least a further 32 weeks of hyperglycaemia and occurred without any significant change in the weight in the tissue. Smaller but significant increases in NA concentration occurred in the glans penis (GP) reaching 150-175% of the control levels during the period of prolonged hyperglycaemia. In contrast, there was no significant change in the NA concentration in the penile urethra. Measurements have also been made that relate to changes in the synthesis and reuptake of NA in the CC during the period during which high NA concentration is maintained. Immunohistochemical studies for the synthetic enzyme tyrosine hydroxylase in the CC indicate that the intensity of staining in the tissue had increased after 10, 20 and 32 weeks of hyperglycaemia, relative to the tissues from control animals. Dilated nerve fibres and engorged endings were present in the CC of the diabetic animals at these times. Reuptake of tritiated NA by the terminal axonal membranes in the CC was raised to 181% of control values after 12 weeks of hyperglycaemia (P<0.05), but later declined to values that are not significantly different from the control levels (after 26 and 64 weeks of hyperglycaemia). There are few studies of the effects of prolonged diabetes on functional aspects of sympathetic postganglionic neurones in the CC, and this paper suggests that the changes described represent remodelling of noradrenergic axonal terminals starting about after 8-10 weeks of hyperglycaemia; this delay in onset of the neuropathic changes is also a feature of type I diabetes in humans.

The effects of age and streptozotocin diabetes on the sympathetic innervation in the rat penis.

The objective was to describe the changes in catecholamine levels, noradrenaline (NA) release and the ultrastructural and immunohistochemical changes in the sympathetic nerves in the penis of STZ-diabetic rats. Amines were measured using HPLC. Nerves were studied using immunocytochemistry for tyrosine hydroxylase, and electron microscopy. Diabetic animals were compared with age-matched controls. The concentration of penile NA increases at least 2.5-fold after about 10 weeks of hyperglycaemia, is maintained for over 40 weeks. The rate of release of NA in the diabetics also increases approximately by fourfold. Immunohistochemical staining for tyrosine hydroxylase showed either no change or an increase in the levels of the enzyme around the central arteries and the outer coverings of the corpus cavernosum. Cavernosal nerves show increased intensity of staining for tyrosine hydroxylase, and the presence of dilated nerve fibres and engorged endings. The axons of the dorsal nerve of the diabetic penis have a smaller cross-sectional area that is most marked in unmyelinated axons. In the diabetic penis, the nerve endings appear to contain significantly more NA than the controls, and the turnover of noradrenaline is increased substantially. There is immunocytochemical evidence of an increase in staining for tyrosine hydroxylase, suggesting an increase in synthetic activity. These results are discussed in relation to the existing literature on the role of amines in normal and disordered erectile function. In particular, the increased concentration and turnover of NA in the diabetic rat contrasts with the fall in NA in cavernosal blood described during normal erection in humans.

New members of the interleukin-12 family of cytokines: IL-23 and IL-27 modulate autoimmune diabetes.

Multiple low doses of streptozotocin (5 x 40 mg/kg) given to susceptible male C57BL6 mice induced delayed and sustained hyperglycemia accompanied by body weight loss, mononuclear cell infiltration in the islet, and apoptosis of beta cells. Shorter regimes (4 x 40 mg/kg) did not have such effect. Administration of IL-23 at a dose of 400 ng/mL for 10 consecutive days concomitantly with this subdiabetogenic regimen of STZ, however, induced significant hyperglycemia, weight loss, and mononuclear cellular infiltration. The same regimen of IL-27 induced milder effect on glycemia and no weight loss inspite of a massive peri-islet and intra-islet infiltration of mononuclear cells. The molecular mechanisms underlying the actions of these cytokines on diabetogenesis is under study.

The superior colliculus of the camel: a neuronal-specific nuclear protein (NeuN) and neuropeptide study.

In this study we examined the superior colliculus of the midbrain of the one-humped (dromedary) camel, Camelus dromedarius, using Nissl staining and anti-neuronal-specific nuclear protein (NeuN) immunohistochemistry for total neuronal population as well as for the enkephalins, somatostatin (SOM) and substance P (SP). It was found that, unlike in most mammals, the superior colliculus is much larger than the inferior colliculus. The superior colliculus is concerned with visual reflexes and the co-ordination of head, neck and eye movements, which are certainly of importance to this animal with large eyes, head and neck, and apparently good vision. The basic neuronal architecture and lamination of the superior colliculus are similar to that in other mammals. However, we describe for the first time an unusually large content of neurons in the superior colliculus with strong immunoreactivity for met-enkephalin, an endogenous opioid. We classified the majority of these neurons as small (perimeters of 40-50 microm), and localized diffusely throughout the superficial grey and stratum opticum. In addition, large pyramidal-like neurons with perimeters of 100 microm and above were present in the intermediate grey layer. Large unipolar cells were located immediately dorsal to the deep grey layer. By contrast, small neurons (perimeters of 40-50 microm) immunopositive to SOM and SP were located exclusively in the superficial grey layer. We propose that this system may be associated with a pain-inhibiting pathway that has been described from the periaqueductal grey matter, juxtaposing the deep layers of the superior colliculus, to the lower brainstem and spinal cord. Such pain inhibition could be important in relation to the camel's life in the harsh environment of its native deserts, often living in very high temperatures with no shade and a diet consisting largely of thorny branches.

Streptozotocin-induced diabetic nephropathy in rats: the role of inflammatory cytokines.

The role of inflammatory cytokines in the pathogenesis of diabetic nephropathy has been studied in streptozotocin-induced diabetic rats. Rat kidneys were examined by light and electron microscopy and kidney homogenates were also analyzed by Western blot and flow cytometry for the expression of markers of inflammation namely, CD4+ and CD8+ T cells, macrophages, MHC classes I and II, the proinflammatory cytokines tumor necrosis factor-alpha, interferon-gamma and nitric oxide (NO). Light and electron microscope examination revealed infiltration of mononuclear cells throughout the renal parenchyma, with the glomeruli being more severely affected especially at 8 months after disease induction. Western blot and flow cytometric analyses revealed the infiltrating cells to be CD4+ T cells, CD8+ T cells and macrophages. Western blot analyses also revealed increased expression of the proinflammatory and Th1 cytokines tumor necrosis factor-alpha, interferon-gamma as well as nitric oxide. Using flow cytometry, we have shown that the difference in expression of CD4+ T cells in control and diabetic kidneys is more significant at 1 month than at 8 months, while expression of CD8+ T cells is more significant at 8 months. We speculate therefore that diabetic nephropathy is probably initiated and driven by a Th1 process. CD8+ T cells, however, become more significant at later stages of the disease when tissue loss is evident. Since NO induction also occurs only after 8 months, we hypothesize that NO might be significant for the later stages of the disease. Our data implicate inflammation in the pathogenesis of diabetic nephropathy in view of the overexpression of the proinflammatory cytokines TNF-alpha and IFN-gamma and the cells that secrete them in the early and late phases of the disease.

Neuroglial response after induction of experimental allergic encephalomyelitis in susceptible and resistant rat strains.

Experimental allergic encephalomyelitis (EAE), the animal model for multiple sclerosis in humans, a T-cell mediated disease of the central nervous system is characterized by inflammatory infiltrates of myelin antigen(s)-specific T cells and consecutive demyelination. Spinal cord tissue emulsified in complete Freund's adjuvant clinical disease in the genetically susceptible Dark Agouti rats (DA) but not in Albino Oxford (AO) rats although similar inflammatory infiltrates in the CNS are observed in both strains 10-12 days after induction. We have shown that the resistance to clinical disease of AO rats is associated with rapid clearance of infiltrating mononuclear cells by a mechanism of apoptosis. Here, we demonstrate by immunohistochemical and FACS analyses of the expression of CD11b/c that microglial cells respond differently to disease induction in the two strains. Whereas microglial cells are activated throughout the period of day 10-28 days after EAE induction in AO rats they are only activated at the inception and resolution phases but not at the peak of clinical disease in DA rats when there is the highest level of CD4+ T cell infiltration. Our findings are compatible with the notion that microglia terminate effector T cells by apoptosis and that lack of this mechanism as evidenced by the lack of CD11b/c expression, support T cell survival and clinical expression of disease.

Effects of ovariectomy and hormone replacement on submucosal collagen and blood vessels of the anal canal of rats.

OBJECTIVE: To study the effects of oestrogen and progesterone on submucosal collagen fibres and vascular plexus of the anal canal. MATERIALS AND METHODS: Experiments were performed on sections of the anal canal of ovariectomized rats following 28 daily subcutaneous injections of 17-beta oestradiol (n = 6, OVX + E, Group 1), medroxyprogesterone acetate (n = 6, OVX + P, Group 2), both drugs (n = 6, OVX + E + P, Group 3) or vehicle (n = 6, OVX) and after sham surgery without castration or injection (n = 6). Investigations included immunohistochemistry of oestrogen and progesterone receptors and collagen fibres, Western blot analysis of collagen types I and III and counting of perianal vessels by light microscopy. RESULTS: There was positive immunostaining for oestrogen and progesterone receptors in the mucosa and for collagen types I and III in the submucosa in all samples. Type I collagen levels increased significantly with ovariectomy but were normalized with treatment with oestrogen and progesterone. Type III collagen levels decreased after ovariectomy. Administration of oestrogen and progesterone appeared to restore level to near sham values. Semi-quantitative measurement of Type I/III collagen ratios by signal intensity demonstrated a very high ratio after ovariectomy. This appeared to be restored by both oestrogen and progesterone administration either individually or in combination. Mean vessel count was significantly lower in sham animals compared to values in OVX animals (P = 0.006). However, while only oestrogen treatment increased significantly the number of vessels compared to sham animals (P = 0.04), replacement with progesterone did not affect and in combination with oestrogen reduced submucosal vessel number. CONCLUSION: Oestrogen and progesterone have synergistic effects on collagen types I and III and probably antagonistic effects on the vascular plexus of the anal canal submucosa in adult female rats.

Effect of foodstuff contamination by aflatoxin on the one-humped camel (Camelus dromedarius) in Al Ain, United Arab Emirates.

Twenty young female adult one-humped racing camels (Camelus dromedarius) kept in camps scattered outside Al Ain city and aged between 3- and 6-years-old, died after a short clinical illness. Affected camels were dull, inappetant and pyrexic, with submandibular oedema and enlargement of submandibular lymph nodes. Of 100 camels within the camps, 31 showed clinical signs. At necropsy examination, the liver of dead animals appeared yellowish, enlarged, congested and friable. The main hepatic histological findings were centrolobular necrosis, haemorrhages and cellular vacuolation. Aflatoxins were detected in sera, liver, ruminal contents and in feed ingested by affected animals. Sera of symptomatic and recovered camels also showed increased levels of glutamic oxaloacetic transaminases, glutamic pyruvic transaminases, aspartate transaminases, gamma glutamyl transaminases, glucose, urea nitrogen, phosphorus and total iron. Decreased levels of albumin, calcium, cholesterol and triglycerides were also observed. It was probable that aflatoxicosis was responsible for clinical signs and subsequent death of the camels. The need for suitable and appropriate storage conditions of animal feed to prevent fungal growth and aflatoxin contamination is highlighted.

Lack of the mediators of innate immunity attenuate the development of autoimmune diabetes in mice.

Interleukin 15 (IL-15) and Interleukin 18 (IL-18) are key cytokines produced by macrophages during innate immune response. These cytokines can profoundly affect subsequent adaptive immune responses including autoimmunity. We have investigated the role of IL-15 and IL-18 in the development of autoimmune diabetes in mice induced by multiple low dose streptozotocin (MLD-STZ). To analyze the role of IL-15, we tested the effects of a soluble murine IL-15 receptor alpha-chain (smIL-15Ralpha), on the development of MLD-STZ in C57BL/6 mice. Animals were treated with 10 daily injections of 32 microg of smIL-15Ralpha starting on the first day of diabetes induction. This treatment significantly attenuated the development of diabetes as evaluated by significantly lower glycemia compared with control mice treated with an inactive mutant form of sIL-15Ra. To directly address the role of IL-18 in MLD-STZ we used IL-18 knockout (KO) mice on DBA/1 background. IL-18 deficient mice were significantly more resistant to the induction of diabetes compared with the wild-type controls and did not develop the typical mononuclear cell infiltrates in the islets. Taken together our data suggest that the innate mediators, IL-15 and IL-18, are essential for the development of diabetes and may be important targets in prevention and early treatment of autoimmune diabetes.

Distribution of insulin like growth factor-1 (IGF-1) and its receptor in the intestines of the one-humped camel (Camelus dromedarius).

The distribution of insulin-like growth factor-1 (IGF-1) and its receptor in the gut of the one-humped camel (Camelus dromedarius) were studied by immunohistochemistry and quantitative receptor autoradiography. IGF-1-IR cells occurred mainly in the lamina propria and epithelium of the small intestine, while in the large intestine positive cells were seen in the columnar cells of the epithelial layer of colonic glands. IGF-I was also discernible in the muscularis externa of the intestines. Autoradiography revealed a higher concentration of receptors in the mucosa compared to the muscular layer. With regard to the mucosa, the highest density of receptors was discernible in the duodenum. Immunohistochemistry revealed the main sites of the receptors to be the lamina propria, epithelia of the crypts and the villi of intestines. Double immunofluorescence studies with combined antisera to IGF-I and its receptor showed that the ligand and its receptor usually occurred within the same cell in the mucosa. A few cells with varied profiles immunoreacted to either the ligand or the receptor but not to both. Cells with varied profiles immunoreacted to antiserum of the receptors but not to the ligand in the muscle layer. Thus IGF-1 might be acting on its receptor via both an autocrine and paracrine modes in the camel mucosa. In the muscularis layer, IGF-1 may be acting by different mechanisms. Our data demonstrate that unlike all other mammals studied, the camel contains a high concentration of IGF-1 receptors in the duodenal mucosa compared to other parts of the camel gut. It also possesses a higher concentration of the receptor in its mucosa compared to the muscle layer. We speculate that this might be a significant feature necessary for the regenerative ability of the duodenal mucosa in the one-humped camel.

Downregulation of apoptosis in the target tissue prevents low-dose streptozotocin-induced autoimmune diabetes.

3,7-dimethyl-1-(5-oxohexyl) xanthine, pentoxifylline (PTX) is shown to affect cytokine-induced apoptosis in several experimental models and clinical conditions. It had been also shown to prevent insulitis and hyperglycemia in non-obese diabetic (NOD) mice, and mice and rats susceptible to diabetes induction with multiple low-doses of streptozotocin (MLD-STZ). We therefore analysed the development of diabetes and apoptosis of pancreatic beta islet cells in CBA/mice after diabetes induction with MLD-STZ. We have evaluated the effect of PTX on the level of apoptosis in the islet at different time intervals after diabetes induction. Complementary histological and immunohistochemical studies and analyses of the expression of cytokines and nitric oxide have also been done. It was concluded that PTX significantly attenuated apoptosis of the beta-cells in the islet and suppressed the induction of diabetes. Our data are compatible with the notion that interferon-gamma (IFN-gamma)/tumor necrosis factor (TNF)/nitric oxide (NO)-induced apoptosis of beta-cells in experimental diabetes is attenuated by PTX.

Loss of kidney IGF-1 receptors in experimental long-term diabetic rats.

The present study was undertaken to assess the long-term effects of streptozotocin-induced diabetes mellitus on insulin-like growth factor-1 (IGF-1) receptors in rat kidneys. Morphological changes were also evaluated using light and electron microscopy. Using receptor autoradiography the levels of IGF-1 were investigated in rat kidneys diabetic for eight months and controls. Sections from both diabetic and control rats were stained with haematoxylin and eosin for morphological studies. Ultra-thin kidney sections were examined using a transmission electron microscope. IGF-1 receptors were significantly lower in the cortex and the medulla of the diabetic rats compared with controls. Morphological differences between normal and diabetic kidneys were observed in both the cortex and medulla. Glomerular changes and necrosis of the renal cortical and medullary parenchyma were demonstrated in the diabetic rats. Necrosis of cells of the collecting ducts and loops of Henle could explain the loss of IGF-1 receptor concentration in the medulla. Shrinkage of glomeruli and normal proximal convoluted tubules of diabetic kidneys were also observed. Our results also revealed extensive damage to the distal convoluted tubules that have not been reported to possess any insulin-like growth factor-1 receptors. Our results demonstrate a reduction of kidney IGF-1 receptors after long-term diabetes mellitus possibly because of the extensive morphological loss of renal tissue. It could be speculated that early administration of IGF-1 might be useful in longterm diabetes mellitus to prevent the degeneration and/or help regeneration of damaged renal tissue.

Neurotransmitters regulating acid secretion in the proventriculus of the Houbara bustard (Chlamydotis undulata): a morphological viewpoint.

Endocrine cells containing somatostatin (Som), gastrin-releasing peptide (GRP), and neuronal nitric oxide synthase (nNOS) and nerve fibers containing choline acetyl transferase (ChAT), tyrosine hydroxylase (TH), galanin (Gal), substance P (SP), and vasoactive intestinal polypeptide (VIP) were immunolocalized in the proventriculus of the Houbara bustard, Chlamydotis undulata. While GRP-immunoreactive (GRP-IR) cells occur in the inner zone, somatostatin (Som-IR) and polyclonal nNOS (nNOS-IR) immunoreactive cells were localized mainly in the peripheral zone of submucosal glands. GRP-IR, Som-IR, and nNOS-IR cells were occasionally observed in the walls of the gastric glands. Endocrine cells are of the closed variety and usually possess apical processes extending along the basal surfaces of adjacent nonreactive cells. Ultrastructural features of these cells are typical. ChAT, Gal, SP, VIP, and TH were immunolocalized in nerve fibers and terminals in the walls of arterioles and capillaries at the periphery of submucosal glands. Immunoreactivity to monoclonal nNOS occurred mainly in neuronal cell bodies in ganglia located around the submucosal glands. ChAT and TH immunoreactive cell bodies were also occasionally seen around the submucosal glands in the peripheral region. Immunoreactivity to Gal, SP, and VIP, but not ChAT or TH, was discernible around the walls of gastric glands. It was concluded that the distribution of neurotransmitters in neuronal structures is similar, but that of the endocrine cells varies from that of some avian species. The roles of these neurotransmitters in the regulation of acid secretion are discussed.

Lack of apoptosis of infiltrating cells as the mechanism of high susceptibility to EAE in DA rats.

Dark Agouti (DA) rats are highly susceptible to induction of Th-1-mediated autoimmunity disease, including experimental allergic encephalomyelitis (EAE). In contrast to other susceptible rat strains in which disease is induced only with encephalitogen emulsified in complete Freund's adjuvants (CFA), in DA rats EAE develops after injection of encephalitogen in incomplete Freund's adjuvants (IFA) or Titermax, putative Th-2 directed adjuvant. Lymph node cells derived from immunized DA rats and stimulated in vitro produce significantly more Interferon-gamma (IFN-gamma) than resistant Albino Oxford (AO) rats. However, cells derived from both strains produce large amounts of IL-10 but not IL-4. Immunized lymph node cells derived from EAE susceptible (AO x DA) F1 rats induce clinical signs of disease in sublethally irradiated parental DA but not AO rats. The pathohistology of the target tissue in these recipients clearly demonstrated infiltration of mononuclear cells in both parental strains. However, the number of CD4+ cells was significantly higher and number of apoptotic cells significantly lower in DA rats sacrificed 8 days after passive transfer. We postulate that in addition to higher IFN-gamma and TNF-alpha production, resistance to early apoptosis of the invading cells in the target tissue possibly due to lack of downregulation by TGF-beta leads to exceptional susceptibility to EAE in DA rats.

Morphological changes in the rat kidney following long-term diabetes.

The morphological basis of diabetic nephropathy has been studied using light and electron microscopy. Kidneys of streptozotocin-induced diabetic rats were examined on the light microscope at 4 weeks and 8 months after induction of diabetes mellitus. In addition, the 8-month diabetic kidneys were examined with the electron microscope. Renal hypertrophy was evidenced by the increase in the weight of kidneys of diabetic rats. Whilst the diabetic kidneys were approximately twice as large after 4 weeks they were only 30% larger compared to age-matched controls after 8 months of induction of diabetes. After 4 weeks, light microscopy revealed dilated tubules within the cortex of the diabetic kidneys. Light microscopy showed a significant amount of destruction of the distal convoluted tubules while electron microscopy revealed a spectrum of damage that included basement membrane thickening, loss of podocytic foot processes, disruption of tubular basal infoldings and their related mitochondria and fibrosis of the tubules 8 months after induction of diabetes. It is concluded that renal hypertrophy persists after a prolonged occurrence of diabetes but the extensive damage and loss of renal tissue including the loss of the foot processes of podocytes might be partly responsible for the clinical presentation of diabetic nephropathy.

Peptidergic hormones and neuropeptides, and aminergic neurotransmitters of the pancreatic islets of the Houbara bustard (Chlamydotis undulata).

Immunoreactivity to insulin (Ins), somatostatin (Som), glucagon (Glu) and pancreatic polypeptide (PP) was found in 70%, 22%, 15% and 11% respectively of Houbara pancreatic endocrine islet cells. Whilst Ins occurred centrally and SOM was observed both in peripherally and centrally located islets, the other hormones were localised in peripheral islet cells; Som was also observed in neuronal cell bodies and nerve fibres. In addition, the islet cells contained substance P (SP) (65%) in the centre and vasoactive intestinal polypeptide (VIP) (2%) at the periphery. Immunoreactivity to choline acetyltransferase (ChAT), VIP and galanin (Gal) occurred in the walls of blood vessels located mainly at the periphery of islets. Occasionally, VIP and Gal immunoreactive varicose nerve terminals and ChAT immunoreactive cell bodies were also observed in the centre of islets. SP neuronal cell bodies were not observed but prominent SP immunoreactive varicose terminals were discernible in capillary walls within the islets. Neuropeptide Y (NPY) immunoreactive neurons were detected in neuronal cell bodies located mainly peripherally. Neuronal nitric oxide synthase (nNOS) immunoreactivity occurred in neuronal cell bodies and nerve fibres mainly at the periphery and also in centrally located islet endocrine cells. Immunoreactivity to tyrosine hydroxylase (TH) was similar in distribution to that of ChAT. In comparison with other avian species, the islets of the dorsal pancreatic lobe of the bustard contain all the peptidergic hormones normally present in the islets of other avian species, but are not segregated into dark A and light B cells. Many of the insulin containing cells also contained SP. The islets also contained several neuropeptides which are probably involved in their regulation.

Peptidergic and aminergic neurotransmitters of the exocrine pancreas of the Houbara bustard (Chlamydotis undulata).

The immunochemical distribution of peptidergic and aminergic neurotransmitters in the exocrine pancreas of the Houbara bustard, Chlamydotis undulata, was determined. Immunoreactivity to choline acetyltransferase (ChAT), vasoactive intestinal polypeptide (VIP), and galanin (Gal) occurred mainly as varicose terminals in the walls of capillaries around the acini and arterioles within the connective tissue. Neuronal cell bodies immunoreactive to ChAT were infrequently observed. Neuropeptide Y (NPY), pancreatic polypeptide (PP), and somatostatin (Som) were observed mainly in intra-acinar cell bodies but nerve fibers immunoreactive to these neuropeptides were also seen along the basal surfaces of the acini. Immunoreactivity to NPY and PP was also discernible in cells of the pancreatic ducts. In addition, NPY occurred as varicose terminals in vessels around the ducts. SP occurred rarely in interacinar ganglia. The distribution of tyrosine hydroxylase (TH) was similar to that of ChAT and, in addition, the occasional TH immunoreactive intra-acinar neuronal cell body was observed. Neuronal nitric oxide synthase (nNOS) occurred in neuronal cell bodies among the acinar cells as well as nerve fibers along the bases of the acini. The potential roles of these peptidergic and aminergic neurotransmitters in the neurohormonal control of pancreatic secretion are discussed.

Renal handling of endogenous human chorionic gonadotrophin in preeclampsia.

OBJECTIVE: To test the hypothesis that the elevated maternal serum concentration of human chorionic gonadotrophin (hCG) in preeclampsia is due to altered renal handling of the hormone. SETTING: Department of Obstetrics and Gynecology, Al Ain Hospital, United Arab Emirates, a tertiary center affiliated with the Faculty of Medicine and Health Sciences, UAE University. METHODS: The renal clearances and handling of endogenous creatinine and human chorionic gonadotrophin were compared in 14 normotensive volunteer and 14 preeclamptic mothers who received oral hydration at 34-37 weeks' gestation. The hCG content in the placentas was estimated immunohistochemically after delivery. RESULTS: Maternal serum concentration of hCG (p = 0.0057), the placental hCG immunopositive cell (p < 0.0001), and syncytial knot counts (p < 0.0001) were significantly higher in preeclamptic mothers. The renal clearances of endogenous creatinine and hCG and fractional hCG clearance were not significantly different in both groups. Significantly increased amounts of hCG were filtered (p = 0.007) and excreted (p = 0.007) by preeclamptic mothers. Only a small but fixed proportion of the filtered load of hCG is excreted in both groups and there was a positive correlation (r = 0.5, p = 0.005) between filtered and excreted loads of hCG. CONCLUSION: The results indicate increased placental content of hCG in preeclampsia. The resultant increased maternal serum concentration is probably sustained by the mechanism of renal handling of the hormone.