Terminology of cell-water relations.

Use of the term "water potential" in place of "diffusion pressure deficit" would improve communication between botanists and scientists in other fields because the concept of potential is familiar to most scientists. Water potential, expressed as PsiW, is the difference in free energy or chemical potential per unit molal volume between pure water and water in cells at the same temperature. The potential of pure water is set at zero; hence the potential of water in cells and solutions is less than zero, or negative. The water potential of a cell is numerically equal to its diffusion pressure deficit, but has a negative sign.

Blockade of mGluR1 receptor results in analgesia and disruption of motor and cognitive performances: effects of A-841720, a novel non-competitive mGluR1 receptor antagonist.

BACKGROUND AND PURPOSE: To further assess the clinical potential of the blockade of metabotropic glutamate receptors (mGluR1) for the treatment of pain. EXPERIMENTAL APPROACH: We characterized the effects of A-841720, a novel, potent and non-competitive mGluR1 antagonist in models of pain and of motor and cognitive function. KEY RESULTS: At recombinant human and native rat mGluR1 receptors, A-841720 inhibited agonist-induced calcium mobilization, with IC50 values of 10.7+/-3.9 and 1.0 +/- 0.2 nM, respectively, while showing selectivity over other mGluR receptors, in addition to other neurotransmitter receptors, ion channels, and transporters. Intraperitoneal injection of A-841720 potently reduced complete Freund's adjuvant-induced inflammatory pain (ED50 = 23 micromol kg(-1)) and monoiodoacetate-induced joint pain (ED50 = 43 micromol kg(-1)). A-841720 also decreased mechanical allodynia observed in both the sciatic nerve chronic constriction injury and L5-L6 spinal nerve ligation (SNL) models of neuropathic pain (ED50 = 28 and 27 micromol kg(-1), respectively). Electrophysiological studies demonstrated that systemic administration of A-841720 in SNL animals significantly reduced evoked firing in spinal wide dynamic range neurons. Significant motor side effects were observed at analgesic doses and A-841720 also impaired cognitive function in the Y-maze and the Water Maze tests. CONCLUSIONS AND IMPLICATIONS: The analgesic effects of a selective mGluR1 receptor antagonist are associated with motor and cognitive side effects. The lack of separation between efficacy and side effects in pre-clinical models indicates that mGluR1 antagonism may not provide an adequate therapeutic window for the development of such antagonists as novel analgesic agents in humans.

Activation of soluble guanylate cyclase causes relaxation of corpus cavernosum tissue: synergism of nitric oxide and YC-1.

Nitric oxide (NO) activates corpus cavernosum smooth muscle soluble guanylate cyclase (sGC) and increases the synthesis of cGMP that results in smooth muscle relaxation and ultimately, penile erection. To characterize sGC and define the potential synergy between NO and the allosteric activator YC-1 in corpus cavernosum, rat sGC was activated by either sodium nitroprusside (SNP) or YC-1, and YC-1 potentiated the effects of SNP with a 200-fold activation of sGC. Both SNP and YC-1 decreased the Km and increased the Vmax. ODQ significantly inhibited sGC activated by SNP with IC50 of 0.5 nM, but did not affect the sGC activated by YC-1 as well as basal sGC activity. SNP and YC-1 synergistically increased intracellular cGMP levels in rabbit corpus cavernosum smooth muscle cell cultures. YC-1 significantly relaxed rabbit cavernosum tissue strips in organ baths with an EC50 of 8.4 microM. In the presence of L-nitroarginine methyl ester to block endogenous NO production, co-administration of SNP shifted the dose response of YC-1 to the left, showing the synergism of SNP and YC-1 in tissue strips. In view of the clinical efficacy of phosphodiesterase-5 inhibitors, activation of sGC may provide an alternative means for enhancing the activity of neurally derived NO during sexual stimulation in the corpus cavernosum, representing a novel approach for the treatment of erectile dysfunction.

Dunaimycins, a new complex of spiroketal 24-membered macrolides with immunosuppressive activity. III. Immunosuppressive activities of dunaimycins.

The immunosuppressive effects of the dunaimycins, a new complex of spiroketal 24-membered macrolides, were compared to cyclosporin A, ascomycin, and rapamycin. Each dunaimycin was a potent inhibitor of the mitogenic response observed in mixed murine splenocyte or human leukocyte cultures, and like immunosuppressive drugs these compounds were relatively less potent inhibitors of the constitutive proliferation of murine EL4 thymoma cells. Dunaimycin D4S showed no selectivity in inhibiting the mitogenic response of spleen cells to concanavalin A, pokeweed mitogen, lipopolysaccharide, or phytohemagglutinin. Cyclosporin A and ascomycin did not inhibit interleukin 2 dependent proliferation, whereas the dunaimycins and rapamycin blocked the uptake of [3H]thymidine in mixed cultures supplemented with exogenous interleukin 2. In addition, dunaimycin D4S had no apparent affinity for cyclosporin A or FK-506 immunophilins. Although the dunaimycins inhibited the activity of Na+, K(+)-ATPase, inhibition of this enzyme appeared insufficient to explain the biological activity of these new macrolides. Over a narrow concentration range, dunaimycin D4S showed in vivo immunosuppressive activity in the murine popliteal lymph node hyperplasia model.

Recognition of feline parovarian nodules as ectopic adrenocortical tissue.

Parovarian nodules encountered during ovariohysterectomy were identified histologically as ectopic adrenocortical tissue. Specimens were examined from 17 healthy female cats aged 6 months to 5 years. The structures were gold to tan, 2 to 5 mm in diameter, and located in the broad ligament within 4 cm of the ovary. Their histologic appearance resembled normal adrenal cortices, with remnants of mesonephric tissue. Adrenal medullary tissue was not found.

Loss to follow-up after arthroplasty: a new use for registry data.

We assessed the outcome of patients who were lost to follow-up after arthroplasty by a single surgeon. The aim was to validate the surgeon's data set with the Australian Orthopaedic Association National Joint Replacement Registry and determine the outcome of those patients lost to follow-up. Prospective data on patient demographics, operative details and outcomes of the surgeon's 1192 primary unicompartmental knee arthroplasty (UKA) procedures were analysed. There were 69 knees in patients who were lost to follow-up, among whom the Registry identified 31 deaths and eight revisions. The cumulative percentage revision (CPR) at seven years using the additional Registry data was 8.8% (95% confidence interval (CI) 7 to 11). Using the surgeon's data, the CPR at seven years was 8% (95% CI 6.3 to 10.1) for the best-case scenario where loss to follow-up was excluded, and 16% (95% CI 13.8 to 19.4) for the worst-case scenario, where all patients lost to follow-up were deemed to have been revised. There was a significantly higher mortality rate in those patients lost to follow-up. This study demonstrates that a national joint registry can be used by individual surgeons to establish more accurate revision rates in their arthroplasty patients. This is expected to facilitate a more rigorous audit of surgical outcomes by surgeons and lead to more accurate and uniform reporting of the results of arthroplasty in general.