Guidance on the treatment of antipsychotic-induced hyperprolactinemia when switching the antipsychotic is not an option.

PURPOSE: This article aims to evaluate management options for antipsychotic-induced hyperprolactinemia and associated treatment considerations such as efficacy, tolerability, drug interactions, contraindications, and dosing regimens. SUMMARY: Hyperprolactinemia is a common adverse effect of antipsychotics. First-line management includes reducing the dose of the offending antipsychotic, discontinuing the antipsychotic, or switching to another antipsychotic associated with a lower risk of hyperprolactinemia. However, these options are not always practical and are associated with a risk of relapse of the psychiatric illness. Other management options include adjunctive aripiprazole, dopamine agonists (cabergoline and bromocriptine), metformin, and herbal supplements. A search of Embase, PubMed, and Google Scholar using key terms such as hyperprolactinemia, prolactin, antipsychotic, treatment guidelines, aripiprazole, dopamine agonist, cabergoline, bromocriptine, metformin, herbals, supplements, and medications was conducted for literature retrieval. Upon evaluation of the available literature we found the following: (1) aripiprazole is safe and effective in lowering prolactin levels within normal limits; (2) adjunctive cabergoline and bromocriptine decrease elevated prolactin levels, while cabergoline may be more effective in reducing prolactin but can also be associated with a more serious adverse effect of cardiac valvular abnormalities; (3) metformin causes a mild reduction of prolactin levels; and (4) there are limited data to support use of herbal medications (chamomile, Peony-Glycyrrhiza decoction, and shakuyaku-kanzo-to) in antipsychotic-induced hyperprolactinemia. CONCLUSION: There are treatments available for antipsychotic-induced hyperprolactinemia in patients who are unable to alter their current antipsychotic regimen. However, there remains a need for additional short- and long-term studies to determine the efficacy and safety of these treatment strategies, given that patients taking antipsychotics typically require chronic, life-long treatment for their illnesses.

The Role of Hormones and Trophic Factors as Components of Preservation Solutions in Protection of Renal Function before Transplantation: A Review of the Literature.

Transplantation is currently a routine method for treating end-stage organ failure. In recent years, there has been some progress in the development of an optimal composition of organ preservation solutions, improving the vital functions of the organ and allowing to extend its storage period until implantation into the recipient. Optimizations are mostly based on commercial solutions, routinely used to store grafts intended for transplantation. The paper reviews hormones with a potential nephroprotective effect, which were used to modify the composition of renal perfusion and preservation solutions. Their effectiveness as ingredients of preservation solutions was analysed based on a literature review. Hormones and trophic factors are innovative preservation solution supplements. They have a pleiotropic effect and affect normal renal function. The expression of receptors for melatonin, prolactin, thyrotropin, corticotropin, prostaglandin E1 and trophic factors was confirmed in the kidneys, which suggests that they are a promising therapeutic target for renal IR (ischemia-reperfusion) injury. They can have anti-inflammatory, antioxidant and anti-apoptotic effects, limiting IR injury.

Prolactin blocks the expression of receptor activator of nuclear factor κB ligand and reduces osteoclastogenesis and bone loss in murine inflammatory arthritis.

BACKGROUND: Prolactin (PRL) reduces joint inflammation, pannus formation, and bone destruction in rats with polyarticular adjuvant-induced arthritis (AIA). Here, we investigate the mechanism of PRL protection against bone loss in AIA and in monoarticular AIA (MAIA). METHODS: Joint inflammation, trabecular bone loss, and osteoclastogenesis were evaluated in rats with AIA treated with PRL (via osmotic minipumps) and in mice with MAIA that were null (Prlr-/-) or not (Prlr+/+) for the PRL receptor. To help define target cells, synovial fibroblasts from Prlr+/+ mice were treated or not with proinflammatory cytokines ((Cyt), including TNFα, IL-1ß, and interferon (IFN)γ) with or without PRL, and these synovial cells were co-cultured or not with bone marrow osteoclast progenitors from Prlr+/+ or Prlr-/- mice. RESULTS: In AIA, PRL treatment reduced joint swelling, increased trabecular bone area, lowered osteoclast density, and reduced mRNA levels of osteoclast-associated genes (tartrate-resistant acid phosphatase (Trap)), cathepsin K (Ctsk), matrix metalloproteinase 9 (Mmp9), and receptor activator of nuclear factor κB or RANK (Tnfrsf11a)), of genes encoding cytokines with osteoclastogenic activity (Tnfa, Il1b, Il6, and receptor activator of nuclear factor κB ligand or RANKL (Tnfrsf11)), and of genes encoding for transcription factors and cytokines related to T helper (Th)17 cells (Rora, Rorc, Il17a, Il21, Il22) and to regulatory T cells (Foxp3, Ebi3, Il12a, Tgfb1, Il10). Prlr-/- mice with MAIA showed enhanced joint swelling, reduced trabecular bone area, increased osteoclast density, and elevated expression of Tnfa, Il1b, Il6, Trap, Tnfrsf11a, Tnfrsf11, Il17a, Il21, Il22, 1 l23, Foxp3, and Il10. The expression of the long PRL receptor form increased in arthritic joints, and in synovial membranes and cultured synovial fibroblasts treated with Cyt. PRL induced the phosphorylation/activation of signal transducer and activator of transcription-3 (STAT3) and inhibited the Cyt-induced expression of Il1b, Il6, and Tnfrsf11 in synovial fibroblast cultures. The STAT3 inhibitor S31-201 blocked inhibition of Tnfrsf11 by PRL. Finally, PRL acted on both synovial fibroblasts and osteoclast precursor cells to downregulate Cyt-induced osteoclast differentiation. CONCLUSION: PRL protects against osteoclastogenesis and bone loss in inflammatory arthritis by inhibiting cytokine-induced expression of RANKL in joints and synovial fibroblasts via its canonical STAT3 signaling pathway.

Efecto de la anestesia local en la respuesta al dolor. Estudio en la herniotomía inguinal / Effect of the local anesthesia in the response to the pain. Study in the inguinal herniotomy

Introducción. La herniotomía inguinal es un procedimiento quirúrgico común en cirugía pediátrica y como en cualquier intervención quirúrgica es fundamental el control del dolor. El objetivo de este estudio es comprobar el efecto de la anestesia local junto a la anestesia general, en el control del dolor postquirúrgico. Material y método. Se realiza un estudio prospectivo en 60 pacientes sometidos a reparación de hernia inguinal e hidrocele unilateral, bajo anestesia general. Los pacientes fueron designados al azar en tres grupos iguales después de la inducción anestésica. En el grupo I se realiza bloqueo ilio-inguinal, antes de la incisión quirúrgica. En el grupo IIse realiza infiltración local tras el cierre de la aponeurosis y en el grupo III no se infiltra anestésico local. La edad de los pacientes estuvo comprendida entre 1 y 13 años. Para la valoración del dolor y comparación entre los tres grupos utilizamos: 1) Mediciones de tipo conductuales.2) Mediciones de tipo biológico antes y después de la intervención: Tensión arterial, frecuencia cardiaca, frecuencia respiratoria… 3)Mediciones de laboratorio: niveles de cortisol, prolactina, insulina y glucosa. Se realizan dos extracciones, la primera después de la inducción anestésica y la segunda 60 minutos después de la intervención. Los resultados fueron analizados empleando el programa informático-estadístico SPSS. Un valor de probabilidad < 0,05 fue considerado significativo. Resultados. 1) Mediciones de tipo conductuales: Las diferencias entre los grupos I y II en relación con el III fueron significativas. Esta diferencia conductual también estuvo relacionada con la edad de los pacientes. 2) Mediciones de tipo biológico. En los grupos I y II la tensión arterial media postoperatoria fue menor, pero solo en el grupo Il a diferencia fue significativa. La frecuencia cardiaca disminuyó en los tres grupos, pero significativa solo en el grupo I, al igual que la frecuencia respiratoria. 3) Mediciones de laboratorio: En los grupos I y II los niveles de cortisol y glucosa disminuyeron en el postoperatorio, pero sólo en el grupo I la diferencia fue significativa. Los valores de prolactina sólo disminuyeron en el postoperatorio en el grupo I pero no fue significativo. La insulina experimentó un aumento en los tres grupos, aunque menor en el grupo I. Conclusiones. 1) Los resultados del estudio demuestran que la infiltración local de anestésico disminuye la respuesta metabólica y reduce la intensidad del dolor postoperatorio, especialmente cuando se realiza antes del comienzo de la cirugía. 2) En la respuesta conductual al dolor no solo influye la utilización de anestésico local si no también la edad del paciente (AU)

Introduction. The inguinal herniotomy is a surgical procedure common in pediátric surgery and as in any operation the control of the pain is fundamental. The aim of this study is to verify the effect of the local anesthesia next to the general anesthesia, in the control of postsurgicalpain. Material and method. A prospective study is made in 60 patients submitted for unilateral repair of hernia inguinal and hydrocele, undergeneral anesthesia. The patients were designated at random in three equal groups after the anesthetic induction. In group I ilio-inguinal blockade is made, before the surgical incision. In group II local infiltration is made after the closing of the aponeurosis and in group III the anesthetic is not infiltrate. The age of the patients included was between 1and 13 years. For the valuation of the pain and comparison between the three groups we used: 1) Measurements of conductual type. 2) Measurements of biological type before and after the intervention: Arterial tension, cardiac frequency, respiratory frequency… 3) Laboratory measurements: cortisol levels, prolactose, insulin and glucose. Two extractions are made, first after the anesthetic induction and second60 minutes after the intervention. The results were analyzed using computer statistical program SPSS. A probability value of < 0,05 was consideredsignificant. Results. 1) Conductual measurements: The differences between groups I and II in relation to the III were significant. This conductual difference also was related to the age of the patients. 2) Measurements of biological type. In groups I and II the postoperative arterial tension average was smaller, but only in group I the difference was significant. The heart rate decreased in the three groups, but was significant only in group I, like the respiratory frequency. 3) Laboratory measurements: In groups I and II the levels of cortisol and glucose diminished in the postoperative period, but only in group I the difference was significant. The values of prolactose diminished in the postoperative period in group I but was not significant. Insulin experienced an increase in the three groups, although smaller in group I. Conclusions. 1) The results of the study demonstrate specially that the local infiltration of anesthetic diminishes the metabolic answer and reduces the intensity of the post operating pain, when is made before the beginning of the surgery. 2) In the conductual answer to the pain not only influences the use of the anaesthetics but the age of the patient (AU)

Monoamine biosynthesis in hypothalamic regions of dwarf mice: effect of replacement of deficient anterior pituitary hormones.

Female Ames dwarf and phenotypically normal female mice were killed 30 min after treatment with NSD-1015, an aromatic L-amino acid decarboxylase inhibitor. The accumulation of dihydroxyphenylalanine (DOPA) and 5-hydroxytryptophan were measured by high-performance liquid chromatography with electrochemical detection and provided estimates of the endogenous biosynthesis of dopamine (DA) in the median eminence (ME) and serotonin biosynthesis (5-HT) in all brain regions which were examined. Dopamine synthesis was markedly suppressed in the ME while 5-HT synthesis was enhanced in both the ME and mediobasal hypothalamus (MBH) of dwarfs as compared to phenotypically normal mice. Overall, catecholamine biosynthesis (DOPA accumulation) was suppressed in the MBH of the dwarf mice but was not different from that observed in normal mice in the preoptic area anterior hypothalamus (POA-AH). The biosynthesis of 5-HT was not different in the POA-AH of dwarf mice as compared to normal mice. In the second experiment dwarf mice received saline vehicle, ovine prolactin (PRL), growth hormone (GH) or thyroxin (T4) daily for 14 days. Normal mice received saline only. Replacement with PRL significantly enhanced DA synthesis in the ME and was the only hormone to suppress significantly the elevation of 5-HT synthesis normally observed in the ME and the MBH of the dwarfs. Both GH and T4 only partially reduced 5-HT synthesis in the ME and MBH so that this parameter was no longer statistically different from either saline-treated dwarfs or normal mice.(ABSTRACT TRUNCATED AT 250 WORDS)

[Pharmacological correction of the disorders of cardiac contractile function in stress]. / Farmakologicheskaia korrektsiia narushenii sokratitel'noi funktsii serdtsa pri stresse.

It has been established that sodium hydroxybutyrate, prolactin, propranolol and ionol are capable of preventing the depression of the contractile function of the heart and of decreasing the glycogen level in the myocardium, provoked by emotional stress.