Milka Jerić

Maternal pre-pregnancy underweight and fetal growth in relation to institute of medicine recommendations for gestational weight gain☆

PURPOSE Maternal nutritional status is one of the most important factors of fetal growth and development. Consequently, the currently increasing prevalence of underweight women worldwide has come in the focus of interest of perinatal medicine. The aim of the study was to assess the effect of low pre-pregnancy body mass index (BMI) on fetal growth. MATERIALS AND METHODS Data on 4678 pregnant women and their neonates were retrospectively analyzed. Pre-pregnancy BMI of study women was categorized according to the WHO standards. Fetal growth was assessed by birth weight and birth length, birth weight for gestational age, and ponderal index. RESULTS Study group included 351 (7.6%) women with pregestational BMI<18.5kg/m(2), while all women with pregestational BMI 18.5-25kg/m(2) (n=3688; 78.8%) served as a control group. The mean birth weight and birth length of neonates born to underweight mothers were by 167g and 0.8cm lower in comparison with the neonates born to mothers of normal nutritional status, respectively (P<0.001 both). The prevalence of small for gestational age (SGA) births was twofold that found in the control group of mothers of normal nutritional status (9.7% vs. 4.9%; P<0.001). The inappropriately low gestational weight gain additionally increased the rate of SGA infants in the group of mothers with low pre-pregnancy BMI (21.4% vs. 10.4%; P=0.02). Pre-pregnancy BMI category did not influence neonatal growth symmetry. CONCLUSION Low maternal pregestational BMI is associated with fetal growth assessment. Improvement of the maternal nutritional status before pregnancy can increase the likelihood of perinatal outcome.

Expression of PTHrP and PTH/PTHrP receptor 1 in the superior cervical ganglia of rats.

PTHrP and its receptor PTHR1 are found in the CNS and peripheral nervous system. The presence of PTHrP mRNA has been detected in the superior cervical ganglion (SCG), but there are no data on the cellular distribution of PTHrP and PTHR1 in the SCG. Although it is known that ovarian activity and reproductive status influence sympathetic activity, and the PTHrP/PTHR1 system is influenced by estrogens in different tissues, it is not known whether these factors have a similar effect on expression of PTHrP and PTHR1 in the nervous system. Hence, we investigated the presence and distribution of PTHrP and PTHR1 in neurons and glia of the SCG of rats, as well as the influence of ovariectomy on their expression, by using immunohistochemistry. PTHrP and PTHR1 immunoreactivity was observed in cytoplasm as well as in nuclei of almost all neurons in the SCG. In male rats, intensity of PTHrP fluorescence was significantly higher in cytoplasm of NPY-, in comparison to NPY+ neurons (p < 0.05). In female rats, 2 months post-ovariectomy, significantly lower intensity of PTHrP fluorescence in cytoplasm of the SCG neurons was observed in comparison to sham operated animals (p < 0.05). In addition to neurons, PTHrP and PTHR1 immunoreactivity was observed in most of the glia and was not influenced by ovariectomy. Results show the expression of PTHrP and its receptor, PTHR1, in the majority of neurons and glial cells in the SCG of rats. Expression of PTHrP, but not PTHR1 in the cytoplasm of SCG neurons is influenced by ovarian activity.

Diabetes mellitus affects activity of calcium/calmodulin-dependent protein kinase II alpha in rat trigeminal ganglia

The activity of calcium/calmodulin-dependent protein kinase II alpha (CaMKIIα) may play a critical role in the modulation of nociceptor activity and plasticity of primary sensory trigeminal neurons. The aim of this study was to investigate the immunoreactivity of phosphorylated CaMKIIα (pCaMKIIα) in subpopulations of trigeminal ganglion (TG) neurons in rat models of early diabetes type 1 (dm1) and 2 (dm2). DM1 model was induced with intraperitoneally (i.p.) injected streptozotocin (STZ) (55mg/kg). DM2 rats were fed with the high fat diet (HFD) for 2 weeks and then received 35mg/kg of STZ i.p. Two weeks and 2 months after the STZ-diabetes induction, rats were sacrificed and immunohistochemical analysis for detection of pCaMKIIα immunoreactivity and double immunofluorescence labelling with isolectin (IB4) was performed. Increased intensity of pCaMKIIα immunofluorescence, restricted to IB4-negative small-diameter neurons, was seen in TG neurons two months after STZ-DM1 induction. DM1 model, as well as the obesity (control dm2 groups) resulted in neuronal impaired growth while dm2 model led to neuron hypertrophy in TG. Observed changes may play a critical role in the modulation of nociceptor activity and plasticity of primary sensory trigeminal neurons. In future, innovative strategies for modulation of CaMKIIα activity in specific subpopulations of neurons could be a novel approach in therapy of diabetic trigeminal neuropathy.

Authors’ lack of awareness and use of core outcome set on postoperative pain in children is hindering comparative effectiveness research

AIM To analyze awareness about and acceptability of core outcome set (COS) for pediatric pain recommended by the PedIMMPACT. METHODS We invited authors of systematic reviews and randomized controlled trials about interventions for postoperative pain in children to participate in a survey. RESULTS Only a third of surveyed authors of systematic reviews and randomized controlled trials about postoperative pain in children had heard about the PedIMMPACT COS for acute pediatric pain. Problems indicated as preventing them from using the COS were lack of awareness, difficulties with implementation, and lack of resources. CONCLUSION Further discussions about the adequacy of COS for acute pediatric pain, as well as interventions to increase the uptake of COS may be warranted.

Diabetes mellitus influences the expression of NPY and VEGF in neurons of rat trigeminal ganglion

BACKGROUND Diabetes mellitus (DM) influences the trigeminal nerve function by changing the pain response and transduction of the orofacial sensory pathways. It affects the inflammatory response via neuropeptide Y (NPY) and vascular endothelial growth factor (VEGF), which could potentially have a relevant role in the pathophysiology of diabetic neuropathy. The aim was to investigate expression of VEGF and NPY in subpopulations of trigeminal ganglion (TG) neurons in rat models of early DM1 and DM2. METHODS DM1 model was induced by an intraperitoneal (i.p.) injection of streptozotocin (STZ) (55mg/kg). DM2 rats were fed with a high fat diet (HFD) for two weeks and then received 35mg/kg of STZ i.p. Two weeks and 2months after the STZ-diabetes induction, rats were sacrificed and TG was immunohistochemically analyzed for detection of VEGF and NPY expression, and also double immunofluorescence labeling with isolectin (IB4) was completed. RESULTS An increased percentage of NPY+ neurons was observed 2weeks after DM1 and 2months post DM2 induction. NPY immunoreactivity was restricted to IB4-negative small-diameter and IB4+ neurons. Two weeks post induction, DM1 rats showed an increased percentage of VEGF/IB4- large neurons and DM2 rats showed an increased percentage of VEGF/IB4+ neurons. Two months after DM induction, the DM1 group showed a reduced percentage of VEGF/IB4- small neurons. CONCLUSION The observed changes may play a critical role in the modulation of nociceptor activity and plasticity of primary sensory trigeminal neurons. The results contribute to the understanding of the basic pathophysiology of trigeminal diabetic neuropathy.

Aging and a long-term diabetes mellitus increase expression of 1 α-hydroxylase and vitamin D receptors in the rat liver

Diabetes mellitus (DM) is a metabolic disorder associated with serious liver complications. As a metabolic chronic disease, DM is very common in the elderly. Recent studies suggest ameliorating effects of vitamin D on metabolic and oxidative stress in the liver tissue in an experimental model of DM. The aim of this study was to investigate the expression of vitamin D receptors (VDRs) and 1α-hydroxylase, the key enzyme for the production of active vitamin D form (calcitriol) in the liver during long-term diabetes mellitus type 1 (DM1) in aging rats. We performed immunohistochemical analysis of liver expression of 1α-hydroxylase and VDRs during aging in long-term streptozotocin-induced DM1. 1α-Hydroxylase was identified in the monocyte/macrophage system of the liver. In addition to the nuclear expression, we also observed the expression of VDR in membranes of lipid droplets within hepatocytes. Aging and long-term DM1 resulted in significant increases in the number of 1α-hydroxylase immunoreactive cells, as well as the percentage of strongly positive VDR hepatocytes. In conclusion, the liver has the capacity for active vitamin D synthesis in its monocyte/macrophage system that is substantially increased in aging and long-term diabetes mellitus. These conditions are also characterized by significant increases in vitamin D receptor expression in hepatocytes. The present study suggests that VDR signaling system could be a potential target in prevention of liver complications caused by diabetes and aging.

Expression pattern of CYP24 in liver during ageing in long-term diabetes.

Association of liver calcitriol (active vitamin D metabolite) catabolism with osteomalacia during prolonged use of certain drugs was reported in several recent studies. To examine whether the increased calcitriol catabolism could be a potential link between ageing/diabetes mellitus (DM) and bone loss, we studied the dynamic of expression of CYP24, the main calcitriol catabolising enzyme in the liver of rats during ageing and a long-term experimental DM1. DM1 model was induced with intraperitoneally injected streptozotocin (STZ) (55mg/kg). Sprague-Dawley rats were sacrificed 6 and 12 months after the DM1 induction. The immunohistochemical analyses of CYP24 and transforming growth factor β 1 (TGF-β1) expression in the liver were performed. We found that ageing and long-term DM1 resulted in a significantly increased expression of CYP24 in hepatocytes, as well as in non-hepatocyte liver cells (Kupffer cells, hepatic stellate cells and sinusoidal endothelial cells). Ageing and long-term DM1 resulted in an increased expression of TGF-β1 as well. Expression of CYP24 coexisted with the expression of TGF-β1 in all types of hepatic cells. We concluded that liver has the capacity for an active vitamin D catabolism in different populations of liver cells, especially in sinusoidal endothelial cells, through an expression of CYP24. That capacity is substantially increased during ageing and long-term diabetes mellitus. Increased liver calcitriol catabolism could be one of the mechanisms of the bone metabolism impairment related to ageing and diabetes.

Outcome domains and pain outcome measures in randomized controlled trials of interventions for postoperative pain in children and adolescents

We analysed outcome domains and pain outcome measures in randomized controlled trials of interventions for postoperative pain management in children and adolescents and compared them to the core outcome set recommended by the Pediatric Initiative on Methods, Measurement and Pain Assessment in Clinical Trials (PedIMMPACT).

Treatment of acute migraine attacks in children with analgesics on the World Health Organization Essential Medicines List: A systematic review and GRADE evidence synthesis

Background The World Health Organization Essential Medicines List (WHO EML) contains two analgesics for treatment of acute migraine attacks in children, ibuprofen and paracetamol. Methods The Embase, CDSR, CENTRAL, DARE and MEDLINE databases were searched up to 18 April 2017. We analyzed randomized controlled trials (RCTs) and systematic reviews (SRs) that investigate the efficacy and safety of ibuprofen or paracetamol for treatment of acute migraine attacks in children. We conducted meta-analysis and assessments of evidence with GRADE, Cochrane risk of bias tool, and AMSTAR. Results Three RCTs (201 children) and 10 SRs on ibuprofen and/or paracetamol for acute migraine attacks in children were included. Meta-analysis indicated that ibuprofen was superior to placebo for pain-free at 2 h or pain relief at 2 h, without difference in adverse events. There were no differences between paracetamol and placebo, or ibuprofen and paracetamol. Ten SRs that analyzed various therapies for migraine in children were published between 2004 and 2016, with discordant conclusions. Conclusion Limited data from poor quality RCTs indicate that ibuprofen and paracetamol might be effective analgesics for treating migraine attacks in children. Inclusion of ibuprofen and paracetamol as antimigraine medicines for children in the WHO EML is supported by indirect evidence from studies in adults.

Poslijeoperacijsko liječenje boli nakon kirurškog liječenja sindroma karpalnog tunela: usporedba prakse sa smjernicama

The management of postoperative pain after carpal tunnel syndrome surgical treatment at a tertiary hospital was analyzed and compared with the guidelines for perioperative pain management. This retrospective study included 579 patients operated on for carpal tunnel syndrome at the Split University Hospital Center in Split, Croatia. The following key data were collected from patient medical records: age, gender, type and dosage of premedication, type and dosage of anesthesia, type and dosage of postoperative analgesia per each postoperative day. The procedures related to perioperative pain were analyzed and compared with the current guidelines for perioperative acute pain management. Study results showed that 99.6% of patients with carpal tunnel syndrome were operated under local anesthesia, of which 2.9% also received sedation. Analgesics were prescribed to 45% of patients after surgery, and according to patient charts, 39% of patients actually received postoperative analgesic(s). Generally, postoperative pain was treated on the fi rst postoperative day, mostly with nonsteroidal anti-inflammatory drugs. Only two patients received weak opioids for postoperative pain. Many recommendations from the guidelines for perioperative acute pain management were not followed. In conclusion, the guidelines should be followed and appropriate interventions used to improve postoperative pain management.