Across and within breed differences in the relationship between packed cell volume and fecal egg count in growing meat goat and hair sheep males naturally and artificially infected with gastrointestinal nematodes.

The relationship between packed cell volume (PCV) and fecal egg count (FEC) in different breeds of meat goats and hair sheep infected with gastrointestinal nematodes, including Haemonchus contortus, was characterized. Growing males from eight commercial and two research farms (one Kiko, Spanish, Dorper, and St. Croix; three Boer; four Katahdin) in the southcentral United States were evaluated in a central performance test with ad libitum intake of a 50% concentrate pelleted diet. There were 84 Boer, 55 Kiko, and 57 Spanish goats and 52 Dorper, 129 Katahdin, and 49 St. Croix sheep. During adaptation, animals were dewormed then dosed with 10,000 infective H. contortus larvae. PCV and FEC were determined before deworming (i.e., natural infection potentially with multiple internal parasites) and 21, 28, 35, 42, and 49 days after artificial infection. Effects of species, breed, and year were analyzed with mixed effects models including day of sampling post dosing as a repeated measure and FEC and FEC × breed as covariates. Moreover, differences in correlation coefficients between PCV and logarithmic FEC (lnFEC) among species, breed, year, and day of sampling were evaluated. Breed affected (P ≤ 0.001) PCV in goats (24.8, 27.2, and 26.0% for Boer, Kiko, and Spanish, respectively; SEM = 0.42) and sheep (29.8, 26.7, and 31.0% for Dorper, Katahdin, and St. Croix, respectively; SEM = 0.28). There were effects of FEC × breed (P ≤ 0.029) on PCV for Boer, Kiko, Dorper, Katahdin, and St. Croix (-0.31, -0.33, -0.46, -0.46, and - 0.49% per 1000 eggs, respectively) but not for Spanish goats (P = 0.451). With all data, PCV and lnFEC with natural infection were highly correlated (P < 0.001) for Boer and Kiko goats and Dorper and Katahdin sheep (r = -0.59, -0.67, -0.77, and - 0.84, respectively) but not for Spanish goats or St. Croix sheep (P ≥ 0.323). Correlation coefficients for artificial infection with H. contortus were significant (P ≤ 0.002) except for Spanish goats, although values were lower (-0.40, -0.21, -0.23, -0.47, and - 0.28 for Boer, Kiko, Dorper, Katahdin, and St. Croix, respectively) compared with natural infection. In conclusion, PCV was not related to FEC in Spanish goats infected either naturally or artificially, and the nature of the relationship varied among breeds of goats and sheep. Based on the magnitude of the FEC × breed coefficient, sheep incurred a relatively greater reduction in PCV as FEC increased, and correlation coefficients indicate stronger relationships with natural than artificial infection.

Degenerative Encephalopathy in Nova Scotia Duck Tolling Retrievers Presenting with a Rapid Eye Movement Sleep Behavior Disorder.

BACKGROUND: Neurodegenerative diseases are a heterogeneous group of disorders characterized by loss of neurons and are commonly associated with a genetic mutation. HYPOTHESIS/OBJECTIVES: To characterize the clinical and histopathological features of a novel degenerative neurological disease affecting the brain of young adult Nova Scotia Duck Tolling Retrievers (NSDTRs). ANIMALS: Nine, young adult, related NSDTRs were evaluated for neurological dysfunction and rapid eye movement sleep behavior disorder. METHODS: Case series review. RESULTS: Clinical signs of neurological dysfunction began between 2 months and 5 years of age and were progressive in nature. They were characterized by episodes of marked movements during sleep, increased anxiety, noise phobia, and gait abnormalities. Magnetic resonance imaging documented symmetrical, progressively increasing, T2-weighted image intensity, predominantly within the caudate nuclei, consistent with necrosis secondary to gray matter degeneration. Abnormalities were not detected on clinicopathological analysis of blood and cerebrospinal fluid, infectious disease screening or urine metabolite screening in most cases. Postmortem examination of brain tissue identified symmetrical malacia of the caudate nuclei and axonal dystrophy within the brainstem and spinal cord. Genealogical analysis supports an autosomal recessive mode of inheritance. CONCLUSIONS AND CLINICAL IMPORTANCE: A degenerative encephalopathy was identified in young adult NSDTRs consistent with a hereditary disease. The prognosis is guarded due to the progressive nature of the disease, which is minimally responsive to empirical treatment.

Clinical medical sciences for undergraduate dental students in the United Kingdom and Ireland - a curriculum.

The technical aspects of dentistry need to be practised with insight into the spectrum of human diseases and illnesses and how these impact upon individuals and society. Application of this insight is critical to decision-making related to the planning and delivery of safe and appropriate patient-centred healthcare tailored to the needs of the individual. Provision for the necessary training is included in undergraduate programmes, but in the United Kingdom and Ireland there is considerable variation between centres without common outcomes. In 2009 representatives from 17 undergraduate dental schools in the United Kingdom and Ireland agreed to move towards a common, shared approach to meet their own immediate needs and that might also be of value to others in keeping with the Bologna Process. To provide a clear identity the term 'Clinical Medical Sciences in Dentistry' was agreed in preference to other names such as 'Human Disease' or 'Medicine and Surgery'. The group was challenged to define consensus outcomes. Contemporary dental education documents informed, but did not drive the process. The consensus curriculum for undergraduate Clinical Medical Sciences in Dentistry teaching agreed by the participating centres is reported. Many of the issues are generic and it includes elements that are likely to be applicable to others. This document will act as a focus for a more unified approach to the outcomes required by graduates of the participating centres and act as a catalyst for future developments that ultimately aim to enhance the quality of patient care.

Effects of stage of lactation and dietary forage level on body composition of Alpine dairy goats.

Multiparous Alpine does (42) were used to determine how stage of lactation and dietary forage level affect body composition. The feeding and body composition portion of the study had a 2 x 3 factorial arrangement of treatments. Eighteen does were fed a 40% forage diet (40F) and 18 received a diet with 60% forage (60F) for approximately 2, 4, or 6 mo of lactation (59 +/- 1.3, 116 +/- 1.0, and 184 +/- 1.4 d, respectively), followed by determination of body composition (6 does per diet at each time of slaughter). Does were assigned sequentially to treatments as kidding occurred. The 60F diet had 20% more dehydrated alfalfa pellets than the 40F diet, with higher levels of corn and soybean meal and inclusion of supplemental fat in the 40F diet. Initial body composition measures were made with 6 other does a few days after kidding (0 mo; 4 +/- 0.6 d). Before parturition, does were fed a 50% concentrate diet free choice. Intake of dry matter was greater for 60F than for 40F, average daily gain tended to be affected by an interaction between diet and month (0, 24, 121, -61, 46, and 73 g), and 4% fat-corrected milk was less in mo 5 to 6 than earlier. Internal fat mass was greatest among times at 6 mo and greater for 40F than for 60F. Mass of the gastrointestinal tract was less for 40F than for 60F and decreased with increasing time in lactation. Concentrations of fat in the carcass (13.8, 13.1, 16.5, 11.2, 11.5, and 14.4%), noncarcass tissues (18.6, 24.2, 33.3, 14.3, 16.5, and 24.5%), and empty body (16.5, 18.7, 25.2, 12.9, 14.1, and 19.5% for 40F at 2 mo, 40F at 4 mo, 40F at 6 mo, 60F at 2 mo, 60F at 4 mo, and 60F at 6 mo, respectively) were affected by stage of lactation and diet. Based on daily change in tissue mass and energy, energy concentration in tissue mobilized or accreted was 16, 20, and 32 MJ/kg in 1 to 2, 3 to 4, and 5 to 6 mo of lactation, respectively. In conclusion, based on tissue mass, more energy was expended by the gastrointestinal tract with 60F than with 40F. Considerable internal fat appeared to be mobilized in early lactation, particularly with the diet moderate to high in forage, with more rapid and a greater magnitude of repletion by does consuming the diet lower in forage. The concentration of energy in tissue mobilized or accreted varied with stage of lactation, being considerably greater at 5 to 6 mo of lactation than earlier.

Effects of breed and diet on growth and body composition of crossbred Boer and Spanish wether goats.

Sixty growing 3/4 Boer x 1/4 Spanish (BS) and Spanish (SP) wethers were used to determine influences of diet and breed on growth and body composition. A pelleted 50% concentrate diet (CD) and a diet based on grass hay (HD) were fed for ad libitum intake. Six wethers of each breed were slaughtered at 0 wk (total of 12). Six wethers of each diet-breed combination were slaughtered at 14 and 28 wk (24 per time) after consumption of the CD or HD. Initial BW of fed wethers were 21.6 and 18.8 kg for BS and SP, respectively (SEM = 0.7). Average daily gain during the entire experiment was influenced by an interaction (P < 0.05) between breed and diet (199, 142, 44, and 50 g/d for BS:CD, SP:CD, BS:HD, and SP:HD, respectively). Carcass mass was greater (P < 0.05) for CD vs. HD (56.2, 56.2, 53.2, and 54.0% of empty BW for BS:CD, SP:CD, BS:HD, and SP:HD, respectively). Mass of the liver (2.11, 1.92, 2.00, and 1.98% of empty BW; SEM = 0.05) and gastrointestinal tract (5.50, 4.83, 8.43, and 8.36% of empty BW for BS:CD, SP:CD, BS:HD, and SP:HD, respectively; SEM = 0.16) tended (P < 0.07) to be influenced by an interaction between breed and diet. Mass of internal fat (12.2, 12.1, 3.4, and 3.4% empty BW for BS:CD, SP:CD, BS:HD, and SP:HD, respectively; SEM = 0.3) differed (P < 0.05) between diets. Energy in the carcass (320, 236, 87, and 79 MJ), noncarcass tissues (318, 237, 77, and 72 MJ), and empty body (638, 472, 164, and 150 MJ) ranked (P < 0.05) BS:CD > SP:CD > BS:HD and SP:HD. Empty body concentration of protein was 18.3, 17.5, 18.3, and 19.7% (SEM = 0.3) and of fat was 24.0, 23.4, 10.8, and 10.3% for BS:CD, SP:CD, BS:HD, and SP:HD, respectively (SEM = 0.6). Energy concentration in accreted tissue was 17.0, 18.7, 16.3, and 6.4 MJ/kg for CD:wk 1 to 14, CD:wk 15 to 28, HD:wk 1 to 14, and HD:wk 15 to 28, respectively (SEM = 1.4). In conclusion, relatively high growth potential of growing Boer crossbred goats with a moderate to high nutritional plane does not entail a penalty in realized growth when the nutritional plane is low. Body composition of growing Boer and Spanish goats is fairly similar regardless of growth rate. For growing meat goats other than with a prolonged limited nutritional plane, an average energy concentration in accreted tissue is 17.3 MJ/kg.

ASAS Centennial Paper: Impact of animal science research on United States goat production and predictions for the future.

Goat research in the United States has increased but at a rate less than that in production. Research on goat meat includes nutritional quality, packaging, color, sensory characteristics, and preslaughter management. Goat skins have value for leather, but quality of goat leather has not been extensively studied. Research in the production, quality, antibiotic residues, and sensory characteristics of goat milk and its products has aided development of the US dairy goat industry. Limited progress has been made in genetic improvement of milk or meat production. There is need to explore applications of genomics and proteomics and improve consistency in texture and functionality of goat cheeses. New goat meat and milk products are needed to increase demand and meet the diverse tastes of the American public. Despite research progress in control of mohair and cashmere growth, erratic prices and sale of raw materials have contributed to further declines in US production. Innovative and cooperative ventures are needed for profit sharing up to the consumer level. Internal parasites pose the greatest challenge to goat production in humid areas largely because of anthelmintic resistance. Study of alternative controls is required, including immunity enhancement via nutrition, vaccination, pasture management such as co-grazing with cattle, and genetic resistance. Similarly, the importance of health management is increasing related in part to a lack of effective vaccines for many diseases. Nutrition research should address requirements for vitamins and minerals, efficiencies of protein utilization, adjusting energy requirements for nutritional plane, acclimatization, and grazing conditions, feed intake prediction, and management practices for rapid-growth production systems. Moreover, efficient technology transfer methods are needed to disseminate current knowledge and that gained in future research.

Technical Note: Effects of tethering on herbage selection, intake and digestibility, grazing behavior, and energy expenditure by Boer x Spanish goats grazing high-quality herbage.

Twenty-four yearling Boer x Spanish goats were used in a crossover experiment to determine the effects of tethering on herbage selection, intake and digestibility, grazing behavior, and energy expenditure (EE) with high-quality herbage. Four 0.72-ha paddocks of wheat (Triticum aestivum) and berseem clover (Trifolium alexandrium) were grazed in the spring. Each paddock hosted 6 animals, 3 with free movement and 3 attached to a 3-m tether that was moved daily and provided access to an area of 28.3 m(2). One animal of each treatment and paddock was used to determine herbage selection, fecal output, or grazing behavior and EE. Herbage DM mass in tethered areas before grazing averaged 2,649 and 2,981 kg/ha in periods 1 and 2, respectively. The CP concentration in ingesta was greater (P < 0.05; 23.1 and 20.3 +/- 0.82%) for free vs. tethered animals, although in vitro true DM digestion (75.7 and 76.5 +/- 1.20%, respectively) did not differ (P > 0.05) between treatments. Intake of ME based on in vitro true DM digestion and fecal output was greater (P < 0.05) for free vs. tethered animals (12.7 and 10.4 +/- 0.89 MJ/d). No treatment effects were observed (P > 0.05) for time spent ruminating or grazing (405 and 366 +/- 42.5 min/d, respectively), although mean EE was greater (P < 0.05) for free vs. tethered animals (633 and 512 +/- 27.4 kJ/kg of BW(0.75) for free and tethered, respectively), with differences (P < 0.05) between treatments at each hour of the day. Tethering animals may be acceptable to model those with free movement for some measures such as ingesta composition but appears inappropriate for others, such as energy metabolism.

Antimuscarinic antibodies in primary Sjögren's syndrome reversibly inhibit the mechanism of fluid secretion by human submandibular salivary acinar cells.

OBJECTIVE: Sjögren's syndrome (SS) is an autoimmune condition affecting salivary glands, for which a clearly defined pathogenic autoantibody has yet to be identified. Autoantibodies that bind to the muscarinic M3 receptors (M3R), which regulate fluid secretion in salivary glands, have been proposed in this context. However, there are no previous data that directly show antisecretory activity. This study was undertaken to investigate and characterize the antisecretory activity of anti-M3R. METHODS: Microfluorimetric Ca2+ imaging and patch clamp electrophysiologic techniques were used to measure the secretagogue-evoked increase in [Ca2+]i and consequent activation of Ca2+-dependent ion channels in individual mouse and human submandibular acinar cells. Together, these techniques form a sensitive bioassay that was used to determine whether IgG isolated from patients with primary SS and from control subjects has antisecretory activity. RESULTS: IgG (2 mg/ml) from patients with primary SS reduced the carbachol-evoked increase in [Ca2+]i in both mouse and human acinar cells by approximately 50%. IgG from control subjects had no effect on the Ca2+ signal. Furthermore, the inhibitory action of primary SS patient IgG on the Ca2+ signal was acutely reversible. We repeated our observations using rabbit serum containing antibodies raised against the second extracellular loop of M3R and found an identical pattern of acutely reversible inhibition. Anti-M3R-positive serum had no effect on Ca2+-dependent ion channel activation evoked by the direct intracellular infusion of inositol 1,4,5-triphosphate. CONCLUSION: These observations show for the first time that IgG from patients with primary SS contains autoantibodies capable of damaging saliva production and contributing to xerostomia. The unusual but not unprecedented acute reversibility of the effects of anti-M3 autoantibodies is the subject of further research.

Congenital heart block associated with undiagnosed maternal Primary Sjögren's Syndrome -- a case report and discussion.

Congenital heart block (CHB) has been linked with Sjögren's Syndrome. This paper reports a case of previously undiagnosed maternal Primary Sjögren's Syndrome (1 degrees SS) that was only discovered following the birth of the patient's first child with CHB. The possible pathophysiological mechanisms underlying CHB associated with 1 degrees SS are discussed.

Hydroxychloroquine therapy in patients with primary Sjögren's syndrome may improve salivary gland hypofunction by inhibition of glandular cholinesterase.

OBJECTIVE: To determine whether (i) cholinesterase activity is increased in the saliva of patients with primary Sjogren's syndrome (pSS), (ii) increased levels of cholinesterase of lymphocyte origin could interfere with the secretory activity of submandibular acinar cells, and (iii) hydroxychloroquine at therapeutic doses could interfere with cholinesterase activity. METHODS: The Ellman method was used to determine the levels of salivary cholinesterase activity and the K(i) of both chloroquine and hydroxychloroquine for serum cholinesterase. The ability of lymphocyte cholinesterase to inhibit the acetylcholine (ACh)-evoked rise in [Ca(2+)](i) in mouse submandibular acinar cells was determined using fura-2 microfluorimetry. RESULTS: Patients with pSS had significantly higher levels of cholinesterase activity in both their unstimulated (P < 0.05) and stimulated saliva (P < 0.0001) compared with control subjects. Lymphocyte cholinesterase was capable of inhibiting the ACh-evoked rise in [Ca(2+)](i). The in vitro K(i) for hydroxychloroquine inhibition of cholinesterase was 0.38 +/- 1.4 microM. CONCLUSION: These data suggest that increased levels of cholinesterase present in the salivary glands of patients with pSS may contribute to glandular hypofunction and provide evidence that the therapeutic enhancement of salivary secretion in patients with pSS by hydroxychloroquine may be mediated by inhibition of glandular cholinesterase activity, although further in vivo investigation is needed.

Putative anti-muscarinic antibodies cannot be detected in patients with primary Sjogren's syndrome using conventional immunological approaches.

OBJECTIVE: To determine whether autoantibodies directed against muscarinic M3 receptors are present in the serum of patients with primary Sjogren's syndrome (pSS), and if so whether these autoantibodies inhibit secretion by intact salivary acinar cells. METHODS: IgG was purified by affinity chromatography using protein G from sera collected from 15 patients with pSS. Antibody detection was by Western blotting, whole-cell enzyme-linked immunosorbent assay (ELISA) and immunoblotting. The antisecretory activity of the IgG faction was determined using fura-2 microfluorimetry to measure changes in intracellular Ca(2+) activity ([Ca(2+)](i)) in human and mouse salivary gland acinar cells and in Chinese hamster ovary (CHO) cells transfected with human M3 receptors (CHO-M3). RESULTS: We found no specific M3 receptor recognition by the IgG fraction obtained from pSS patients using either Western blotting or ELISA or immunoblot techniques in which epitope conformation were preserved. Chronic exposure to pSS IgG had no effect on agonist-evoked Ca(2+) signals measured in human or mouse submandibular acinar cells or in CHO-M3 cells. However, acute application of IgG from Sjogren's syndrome patients produced a rapidly reversible reduction in the agonist-stimulated elevation in [Ca(2+)](i). CONCLUSION: These data represent the first demonstration of salivary acinar cell inhibition by pSS IgG; however, this inhibition was found to be reversible. Our data also show that pSS IgG binding to M3R cannot be visualized by conventional immunological approaches.

Dental management of the myasthenic patient.

Myasthenia gravis (MG) is an auto-immune disorder of neuromuscular transmission which results in weakness and fatigue of skeletal muscles. The defect in neuromuscular transmission is most commonly seen in the muscles of the eyes, face, neck and shoulders but, in some patients, the respiratory muscles are involved. Patients with this condition may present with problems that necessitate special consideration when managing their dental treatment. Patients who are only mildly affected by MG can be treated in general dental practice for routine care. There are no contra-indications to the use of local anaesthetic agents and the presence of a vasoconstrictor is desirable. More severely affected patients and those who are very anxious about dental treatment should be cared for within the hospital environment. In these patients, respiratory muscles may be affected and, as a result, a myasthenic crisis may arise which requires assisted ventilation and, in some cases, intubation. Those patients who are fearful of the dental environment are likely to be emotionally stressed during such times and this increases the risk of a myasthenic crisis; sedation techniques can be beneficial in this group of patients.

Effects of different management practices on preweaning and early postweaning growth of Alpine kids.

Two sets of 40 dairy goat Alpine kids (3-9 days of age) were used to determine effects of group versus individual pens, preweaning access to forage and different milk feeding restriction regimens on preweaning and early postweaning growth. Treatments in the first experiment were: C1: individual pens; C2: two kids per pen; P: group pen; and PF: P plus free access to alfalfa hay. Treatment did not affect ADG gain in the 8-week preweaning phase (167, 173, 167 and 168g per day; S.E.=4.5) or in week 1-12 (137, 134, 149 and 128g per day for C1, C2, P and PF, respectively; S.E.=6.7). Treatments in the second experiment were: AL: ad libitum milk intake with two meals in week 3-8, then 50% of intake on the preceding few days with one meal in week 9-10; R-1X and R-2X: 75% of intake on the last few days of week 2 with one or two meals, respectively, in week 3-8, then, 50% intake with one meal in week 9-10; and R-2X-1X: 75% intake with two meals in week 3-6, then 37.5% intake with one meal in week 7-10. Milk DM intake in week 1-10 was greatest (P<0.05) among treatments for AL (174, 115, 128 and 113g per day for AL, R-2X, R-1X and R-2X-1X, respectively). Starter diet DM intake (g per day) was 51, 78, 72 and 143 in week 7-8 (S.E.=16); 138, 194, 165 and 249 in week 9-10 (S.E.=15); 343, 396, 388 and 417 in week 11-12 (S.E.=47); and 508, 530, 489 and 539 in week 13-14 (S.E.=38) for AL, R-2X, R-1X and R-2X-1X, respectively. ADG (g per day) was 139, 120, 119 and 131 in week 1-10 (S.E.=7) and 105, 109, 123 and 117 in week 11-14 (S.E.=16) for AL, R-2X, R-1X and R-2X-1X, respectively. In conclusion, although group pens and forage access may not enhance ADG of artificially reared dairy goat kids by promoting early dry feed consumption restricted feeding regimens can yield preweaning and early postweaning ADG comparable to ad libitum milk intake. Also, feeding milk in restricted amounts once daily appears feasible, and a second reduction in milk intake in the latter part of the suckling phase may further stimulate dry feed intake.

Dairy goat performance with different dietary concentrate levels in late lactation.

Alpine yearling doelings (22; 44+/-1.0kg) and mature does (25; 59+/-1.7kg) were used in an experiment with 16 weeks in late lactation, 8-13 weeks dry and 12 weeks in the subsequent lactation. Diets of 20, 35, 50 or 65% concentrate and 2.18, 2.34, 2.49 and 2.62Mcal/kg ME, respectively (20C, 35C, 50C and 65C treatments, respectively), were consumed ad libitum in late lactation, with a 35% concentrate diet (2.18Mcal/kg ME) in the first 4 weeks of the dry phase and 50% concentrate (2.65Mcal/kg ME) until kidding. Other goats consuming 20 or 35% concentrate in late lactation received 65 (2.65Mcal/kg ME) or 50% concentrate, respectively, in the dry phase (20A and 35A treatments, respectively). All goats consumed a 50% concentrate diet (2.42Mcal/kg ME) in the subsequent early lactation. DM intake in late lactation was similar among treatments (1.95, 2.21, 2.17, 2.10, 1.99 and 2.00kg per day for 20C, 35C, 50C, 65C, 20A and 35A, respectively; S.E.=0.098) and greater (P<0.05) for does versus doelings (2.16 versus 1.98kg per day; S.E.=0.058); DM intake in the dry phase was similar among treatments. Relative to BW, DM intake was greater (P<0.05) for doelings than for does in late lactation (4.16 versus 3.43% BW) and early lactation (4.56 versus 3.80% BW). The effect of dietary treatment on milk production in late lactation varied with parity (P<0.05); milk production by doelings was 1.39, 1.49, 1.43, 1.57, 1.29 and 1.52kg per day and by does was 1.01, 1.89, 2.38, 1.63, 1.17 and 1.34kg per day for 20C, 35C, 50C, 65C, 20A and 35A, respectively; S.E.=0.200). BW change during the entire 16 weeks late lactation phase was greater (P<0.05) for 65C than for other treatments except 50C (6.9, 5.6, 9.1, 10.4, 5.8 and 4.0kg for 20C, 35C, 50C, 65C, 20A and 35A, respectively; S.E.=1.28), although BW at kidding and litter weight were similar among treatments. BW, DM intake and milk production in the first 12 weeks of the subsequent lactation were not affected by dietary treatment or parity. In conclusion, with moderate to high quality forage in late lactation and a moderate level of concentrate in the dry period, the level of concentrate fed in late lactation and in the dry period may not affect subsequent lactation performance regardless of parity. Milk production by doelings in late lactation appears relatively less responsive to dietary concentrate level than that by does.

Acetylcholine-evoked calcium mobilization and ion channel activation in human labial gland acinar cells from patients with primary Sjögren's syndrome.

Recent evidence has indicated that the salivary gland dysfunction associated with Sjögren's syndrome (SjS) is not necessarily due to immune-mediated destruction of acinar tissue. SjS sufferers may possess substantial reserves of acinar tissue but nevertheless be incapable of maintaining salivary flow rates in the normal range. We have investigated the ability of isolated labial gland acinar cells from SjS patients to fluid secrete by measuring agonist-evoked changes in intracellular Ca(2+) ([Ca(2+)](i)) using fura-2 microfluorimetry and activation of K(+) and Cl(-) channels using the patch-clamp whole cell technique. We can confirm that stimulation with a super-maximal dose of acetylcholine (ACh) increased [Ca(2+)]i equally in both control acinar cells and those derived from SjS patients. However, at submaximal concentrations, the dose-response curve for ACh was shifted to the right by approximately one order of magnitude in acinar cells from SjS patients compared to control acinar cells. Patch-clamp measurements consistent with the presence of Ca(2+)-activated K(+) and Cl(-) conductances were obtained from both control acinar cells and those obtained from SjS patients. Dose-dependent activation of the ion channels by acetylcholine was also right-shifted in acinar cells from SjS patients compared to control cells. Our data show that labial gland acinar cells from SjS patients were capable of responding to agonist stimulation by mobilizing [Ca(2+)](i) and activating K(+) and Cl(-) channels consistent with the requirements of fluid secretion. However, the persistent loss of sensitivity to ACh observed in from SjS patients may account for the lack of saliva production observed in these patients in vivo.

A comparison of salivary gland hypofunction in primary and secondary Sjögren's syndrome.

OBJECTIVE: A commonly held view by clinicians is that the salivary gland hypofunction associated with primary Sjögren's syndrome (SS-1) is more severe than that associated with secondary Sjögren's syndrome (SS-2). This study aimed to determine if this view could be substantiated, when applied to a large sample group. METHOD: Unstimulated and paraffin wax-stimulated whole salivary flow rates were retrospectively compared for age and gender matched, patients diagnosed with SS-1 or SS-2 according to the preliminary European criteria. The patients had attended the Xerostomia Clinic, in the Oral Medicine Department, at the Liverpool University Dental Hospital. RESULTS: Sixty-seven patients with SS-1 (average age 57.1 years) were matched with 67 patients with SS-2 (average age 57.6 years), according to gender and age, within 5 years. The mean unstimulated whole salivary flow rates (+/- s.d.) for patients with SS-1 and SS-2 were 0.11 (+/- 0.15) and 0.12 (+/- 0.18) mL min-1 respectively. The mean paraffin wax stimulated, whole salivary flow rates (+/- s.d.) for patients with SS-1 and SS-22 were 0.45 (+/- 0.02) and 0.47 (+/- 0.49) mL/min-1 respectively. No significant differences, in either stimulated (P = 0.54) or unstimulated (P = 0.60) whole salivary flow rates were found between individuals with SS-1 or SS-2. CONCLUSION: The severity of salivary gland hypofunction does not appear to be related to the clinical variant of Sjögren's syndrome.

The role of academic discipline and gender in high school teachers' AIDS-related knowledge and attitudes.

Adolescents represent the fastest growing segment of HIV+ individuals in the United States. Therefore, high school teachers should be both knowledgeable of and comfortable with issues related to HIV/AIDS. This study examined high school teachers' AIDS-related knowledge and attitudes. One hundred forty-one high school teachers from nine central Massachusetts high schools participated. Participants completed the "HIV/AIDS Knowledge and Attitudes Scales for Teachers," as well as questions regarding their teaching experience and academic disciplines. Results indicated a direct relationship between teachers' knowledge of HIV/AIDS and positive or supportive attitudes toward HIV/AIDS. Significant differences were found based on academic discipline, with allied health teachers scoring significantly higher on the knowledge scale than teachers in any other discipline. Specific examples are discussed, as is the need for increased teacher training and comprehensive AIDS education.

An investigation of interactions between the immune system and stimulus-secretion coupling in mouse submandibular acinar cells. A possible mechanism to account for reduced salivary flow rates associated with the onset of Sjögren's syndrome.

OBJECTIVES: To determine whether chronic exposure to lymphocyte-derived cytokines could inhibit the fluid secretory mechanism in salivary gland acinar cells and so account for the loss of gland function seen in the early stages of Sjögren's syndrome. METHODS: Mouse submandibular acinar cells maintained in primary culture were exposed to a profile of cytokines produced by concanavalin A-activated splenic lymphocytes in vitro for periods up to 72 h. Agonist-evoked changes in intracellular Ca(2+) were determined microfluorimetrically in both control and cytokine-treated cells. RESULTS: Acinar cells maintained in primary culture in the presence of cytokines for up to 72 h were able to mobilize intracellular calcium in response to stimulus by acetylcholine in an identical fashion to those maintained in primary culture in the absence of cytokines. Acute application of the conditioned medium produced by the activated lymphocytes had an antisecretory effect on acetylcholine-evoked Ca(2+) mobilization, which was found to be mediated by cholinesterase rather than by cytokines. CONCLUSION: Neither chronic nor acute exposure to the profile of cytokines released by concanavalin A-activated splenic lymphocytes interfered in any way with the second messenger cascade and fluid and electrolyte secretion in acinar cells. Our data suggest an alternative hypothesis, in which elevated levels of cholinesterase can metabolize acetylcholine released within the salivary glands and thus prevent fluid secretion.