Therapeutic efficacy of undenatured type-II collagen (UC-II) in comparison to glucosamine and chondroitin in arthritic horses.

The present investigation evaluated arthritic pain in horses receiving daily placebo, undenatured type II collagen (UC-II) at 320, 480, or 640 mg (providing 80, 120, and 160 mg active UC-II, respectively), and glucosamine and chondroitin (5.4 and 1.8 g, respectively, bid for the first month, and thereafter once daily) for 150 days. Horses were evaluated for overall pain, pain upon limb manipulation, physical examination, and liver and kidney functions. Evaluation of overall pain was based upon a consistent observation of all subjects during a walk and a trot in the same pattern on the same surface. Pain upon limb manipulation was conducted after the walk and trot. It consisted of placing the affected joint in severe flexion for a period of 60 sec. The limb was then placed to the ground and the animal trotted off. The response to the flexion test was then noted with the first couple of strides the animal took. Flexion test was consistent with determining clinically the degree of osteoarthritis in a joint. Horses receiving placebo showed no change in arthritic condition, while those receiving 320 or 480 or 640 mg UC-II exhibited significant reduction in arthritic pain (P < 0.05). UC-II at 480 or 640 mg dose provided equal effects, and therefore, 480 mg dose was considered optimal. With this dose, reduction in overall pain was from 5.7 +/- 0.42 (100%) to 0.7 +/- 0.42 (12%); and in pain upon limb manipulation from 2.35 +/- 0.37 (100%) to 0.52 +/- 0.18 (22%). Although glucosamine and chondroitin treated group showed significant (P < 0.05) reduction in pain compared with pretreated values, the efficacy was less compared with that observed with UC-II. In fact, UC-II at 480 or 640 mg dose was found to be more effective than glucosamine and chondroitin in arthritic horses. Clinical condition (body weight, body temperature, respiration rate, and pulse rate), and liver (bilirubin, GGT, and ALP) and kidney (BUN and creatinine) functions remained unchanged, suggesting that these supplements were well tolerated.

Developmental changes in short-term synaptic depression in the neonatal mouse spinal cord.

We examined age-dependent changes in short-term synaptic depression of monosynaptic excitatory postsynaptic potentials (EPSPs) recorded in lumbar motoneurons in hemisected spinal cords of neonatal Swiss-Webster mice between postnatal day 2 (P2) and 12 (P12). We used four paradigms that sample the input-output dependence on stimulation history in different but complementary ways: 1) paired-pulse depression; 2) steady-state depression during constant frequency trains; 3) modulation during irregular stimulation sequences; and 4) recovery after high-frequency conditioning trains. Paired-pulse synaptic depression declined more than steady-state depression during 10-pulse trains at frequencies from 0.125 to 8 Hz in this age range. Depression during sequences of irregular stimulations that more closely mimic physiological activation also declined with postnatal age. On the other hand, the overall rate of synaptic recovery after a 4-Hz conditioning train exhibited surprisingly little change between P2 and P12. Control experiments indicated that these observations depend primarily, if not exclusively, on changes in presynaptic transmitter release. The data were examined using quantitative models that incorporate factors that have been suggested to exist at more specialized central synapses. The model that best predicted the observations included two presynaptic compartments that are depleted during activation, plus two superimposed processes that enhance transmitter release by different mechanisms. One of the latter produced rapidly-decaying enhancement of transmitter release fraction. The other mechanism indirectly enhanced the rate of renewal of one of the depleted presynaptic compartments. This model successfully predicted the constant frequency and irregular sequence data from all age groups, as well as the recovery curves following short, high-frequency tetani. The results suggest that a reduction in release fraction accounts for much of the decline in synaptic depression during early postnatal development, although changes in both enhancement processes also contribute. The time constants of resource renewal showed surprisingly little change through the first 12 days of postnatal life.

The Ross operation in a Jehovah's Witness: a paradigm for heart surgery in children without transfusion.

A 3-year-old 18 kg male child of the Jehovah's Witness faith presented with severe aortic regurgitation. A successful Ross procedure was performed using a pulmonary autograft, without the use of blood or blood product transfusion. Blood conservation strategy included: (1) preoperative treatment with recombinant human erythropoietin; (2) intraoperative strategies, including technical modifications to the Ross procedure, and the prophylactic use of fibrin glue; (3) utilization of a heparin-bonded cardiopulmonary bypass circuit and assisted venous drainage; and 4) the use of prebypass phlebotomy, cell-saving device and autotransfusion. The patient was discharged home on postoperative day 7 with a hemoglobin level of 11.9.

Endo16, a large multidomain protein found on the surface and ECM of endodermal cells during sea urchin gastrulation, binds calcium.

Endo16 encodes a developmentally regulated protein restricted to cells participating in the formation of the archenteron during sea urchin gastrulation and to the stomach of the pluteus. The 4680-nt coding region of the Endo16 gene has been sequenced from overlapping cDNAs. Sequence analysis revealed that Endo16 is a large multidomain protein starting with a putative signal sequence at its amino terminus which is followed by a cysteine-rich region, two potential heparin-binding regions, an acidic domain of 5 clustered repeats, an RGD cell binding motif, and a group of 12 additional acidic repeats. Immunolocalization by confocal and electron microscopy demonstrate that the Endo16 protein is in the extracellular matrix and associated with the surface of endodermal cells in the mid and hindgut of the archenteron. The two distinct acidic repeat regions are similar to known calcium-binding sequences. A recombinant Endo16 protein containing both putative calcium-binding repeat regions has been shown to bind radioactive calcium. Tryptic digests of gastrula stage protein extracts in the presence and the absence of calcium have established that calcium stabilizes Endo16 protein against proteolytic degradation.

Antigen-presenting liposomes are effective in treatment of recurrent herpes simplex virus genitalis in guinea pigs.

The therapeutic and immunologic effects of a liposome preparation containing both a macrophage activator, muramyl-tripeptide-phosphatidylethanolamine, and a recombinant antigen, glycoprotein D of herpes simplex virus type 1, have been investigated. This preparation was tested in vitro for the ability to stimulate peripheral blood lymphocytes and in vivo for the control of recurrent herpes genitalis in guinea pigs. Our results show that the liposome-antigen-adjuvant preparation is capable of enhancing antigen-specific lymphocyte stimulation, which may be related to the observed 75% suppression of the frequency and severity of reactivation of recurrent herpes simplex virus type 2 genitalis compared with that of placebo controls.

The effect of adjuvants on the efficacy of a recombinant herpes simplex virus glycoprotein vaccine.

A recombinant, truncated HSV type 1 glycoprotein D secreted by Chinese hamster ovary cells (rgD1) was used to compare the ability of several adjuvants to stimulate protective immunity in guinea pigs. Adjuvants tested included CFA, aluminum hydroxide (alum), a lipophilic derivative of muramyl tripeptide (MTP-PE), and a muramyl dipeptide (MDP) covalently conjugated to rgD1. Animals were immunized three times with rgD1 plus the various adjuvants and antibody titers were determined by ELISA. Four weeks after the last immunization, the animals were challenged intravaginally with HSV type 2 and were monitored daily for clinical signs of disease, including frequency and severity of herpetic lesions, incidence of urinary retention, and mortality during the 14-day post-challenge observation period. Animals immunized in the foot-pad with rgD1 formulated with CFA showed the highest antibody titers. Animals immunized in the footpad with rgD1 using MTP-PE in a 4% squalene formulation, alum, or rgD1 conjugated to MDP showed mean antibody titers that were 57, 16, and 13% of the CFA titers, respectively. Immunization with rgD1 plus MTP-PE, alum, or rgD1-MDP conjugate by the i.m. route elicited lower antibody titers than the footpad route of immunization. Results of the viral challenge indicated that clinical symptoms of the groups immunized with rgD1 with CFA or MTP-PE as adjuvant were similar in magnitude and were markedly reduced compared with unimmunized control groups. Animals immunized with rgD1 combined with alum or rgD1-MDP conjugate showed clinical symptoms significantly more severe than the CFA or MTP-PE groups. The protective immunity observed after i.m. immunization of animals with rgD1 and MTP-PE was only slightly lower than animals immunized with the same Ag-adjuvant combination in the footpad. The results indicate that MTP-PE is an effective adjuvant for the recombinant herpes gD vaccine.

The effect of intravenous, subcutaneous, and intranasal GH-RH analog, [Nle27]GHRH(1-29)-NH2, on growth hormone secretion in normal men: dose-response relationships.

A 29 amino acid analog of growth hormone releasing hormone (GH-RH)-40 was given intravenously, subcutaneously, and intranasally to normal men to determine its effectiveness in stimulating growth hormone (GH) release. The GH-RH analog, [Nle27]GH-RH(1-29)-NH2, is an amidated 29 amino acid peptide that has one amino acid substitution at position 27. This peptide stimulates GH secretion when given by the intravenous, subcutaneous, and intranasal routes without adverse effect. The degree of GH stimulation was variable among subjects and the greatest amount of stimulation occurred with the highest doses. GH stimulation occurred in a dose-responsive manner after all three routes of administration. A tenfold higher subcutaneous dose was required to stimulate a comparable amount of GH secretion as compared with intravenous administration, and a thirtyfold higher intranasal than intravenous dose was required to stimulate approximately one fifth the amount of GH release. For comparison, one dose of GH-RH-40, 1 microgram/kg, was administered intravenously. GH secretion after 1 microgram/kg GH-RH-40 and 1 microgram/kg Nle27 GH-RH was comparable between the two groups of subjects. Stimulation of GH secretion by Nle27 GH-RH occurred within 5 minutes of intravenous and within 10 minutes of subcutaneous and intranasal administration; peak GH levels were observed within 30 minutes. GH levels declined and returned to near baseline levels 2 hours after administration of the analog.(ABSTRACT TRUNCATED AT 250 WORDS)

Management of a broken anesthetic injection needle in the maxilla.

The implications of a broken needle in the posterior part of the maxilla are discussed in the context of a case report. Preventive measures and treatment suggestions also are outlined for the practitioner.

Efficacy of EMG biofeedback in relaxation training: a controlled stury.

Electrical activity in the right elbow flexors has been shown to have a high relationship with a general resting muscular tension factor. It was our purpose to evaluate the efficacy of EMG biofeedback in reducing electrical activity in this muscle group. It was found that EMG voltages were significantly reduced (P less than 0.001) due both to biofeedback treatment and to time of day (construed as a practice and/or restbreak effect). Replication of the experiment without biofeedback and designed to minimize the "restbreak" effect induced by repetitive testing produced no change in the EMG voltages. It was concluded that EMG biofeedback training is effective with the elbow flexor group, and the possibility for training subjects in overall deep relaxation through feedback from this one muscle group is suggested. The importance of the practice effect/restbreak is emphasized.