The role of L-carnitine in treatment of a murine model of asthma

Leukotrienes, one of the mediators of inflammation in asthma, have a strong bronchoconstrictive effect. L-carnitine has been reported to influence respiratory functions. It has also been reported that L-carnitine inhibits leukotriene synthesis. To evaluate the effects of L-carnitine on oxygen saturation, urine leukotriene E4 levels and lung histopathology in a murine model of asthma, high IgE responder BALB/c mice (n = 24) were systemically sensitized to ovalbumin and chronically challenged with low particle mass concentrations of aerosolized ovalbumin, and then they were divided into 3 groups (study groups A, B, and C) each including eight mice. After methacholine-induced bronchoconstriction, the mice in groups A and B were given intraperitoneal L-carnitine (250 and 125 mg/kg, respectively), while the mice in group C were given placebo. Oxygen saturation of the mice was measured by pulse oxymeter before and after methacholine and after L-carnitine/ placebo application. In addition, urine leukotriene E4 levels were measured before asthma development, and 24-h after L-carnitine injection in asthmatic mice. Inflammation in the lung tissues of the sacrificed animals was scored histopathologically to determine the effect of L-carnitine on tissue level. A control group of non-sensitized mice (n = 8) treated with placebo only was used for comparison of urine leukotriene E4 levels and of histopathological parameters. Oxygen saturation of the mice in the study groups tended to decrease after methacholine and to improve after L-carnitine injection, although these changes were not significant at all time points. Urine leukotriene E4 levels of all 3 study groups increased significantly after asthma development. The rate of increment was smallest in the group given the highest L-carnitine dose (group A). Inflammation at the tissue level was also mildest in group A, and severest in the group that was not given carnitine (group C). All of the study groups and the control group differed significantly with respect to inflammation scores. In conclusion, L-carnitine improved oxygen saturation, and decreased urine leukotriene E4 levels and inflammation in lung tissues in the present murine model of asthma.     

Exposure to dipeptidyl-peptidase-4 inhibitors and COVID-19 among people with type 2 diabetes: A case-control study

Because other coronaviruses enter the cells by binding to dipeptidyl-peptidase-4 (DPP-4), it has been speculated that DPP-4 inhibitors (DPP-4is) may exert an activity against severe acute respiratory syndrome coronavirus 2. In the absence of clinical trial results, we analysed epidemiological data to support or discard such a hypothesis. We retrieved information on exposure to DPP-4is among patients with type 2 diabetes (T2D) hospitalized for COVID-19 at an outbreak hospital in Italy. As a reference, we retrieved information on exposure to DPP-4is among matched patients with T2D in the same region. Of 403 hospitalized COVID-19 patients, 85 had T2D. The rate of exposure to DPP-4is was similar between T2D patients with COVID-19 (10.6%) and 14 857 matched patients in the region (8.8%), or 793 matched patients in the local outpatient clinic (15.4%), 8284 matched patients hospitalized for other reasons (8.5%), and when comparing 71 patients hospitalized for COVID-19 pneumonia (11.3%) with 351 matched patients with pneumonia of another aetiology (10.3%). T2D patients with COVID-19 who were on DPP-4is had a similar disease outcome as those who were not. In summary, we found no evidence that DPP-4is might affect hospitalization for COVID-19.     

An epidemiological study investigating the relationship between chorangioma and infantile hemangioma

Objectives

This study aimed to verify whether the infantile hemangioma (IH) incidence in children whose placentas showed a chorangioma is higher than in the general population, thus addressing the hypothesized relationship between chorangioma and IH.

Methods

All chorangioma diagnoses by the 1st Service of Pathology, University of Padova in 2004–2010, based on the analysis of placentas sent by the Department of Gynecological Sciences and Human Reproduction (University of Padova), were identified. Demographic, anamnestic and clinical data were collected from the mothers and newborns; mothers and pediatricians were interviewed by telephone within 1 year after birth to verify if any IH appeared. The incidence rates of IH and other adverse events (IUGR, preterm delivery, cesarean section, stillbirth) were compared with national and regional data, when available, or with estimates from the scientific literature.

Results

Thirty-eight chorangioma diagnoses were found. Of 33 infants born with a placenta affected by chorangioma, 18 infants had IH. The IH incidence recorded in our series (55%) was significantly higher than that recorded in national and regional surveys and in the scientific literature. Similar findings have been observed for the incidence of stillbirth, preterm birth and low birth weight incidence.

Conclusions

The IH incidence observed in our series appears to be significantly higher than that recorded among the general population, suggesting that an association between placental chorangioma and IH could exist which should be further verified in prospective studies.     

Characterization and physical stability of fast-dissolving microparticles containing nifedipine.

The suitability of a poly(sodium methacrylate, methyl methacrylate) (NaPMM), a novel mucoadhesive material, to prepare fast-dissolving microparticles containing nifedipine (NIF) in the range of 25-75% w/w was verified. Microparticles made of a low-viscosity hydroxypropylmethylcellulose (HPMC), were also prepared to compare the NIF release profile and bioadhesive properties. The release test was carried out in oversaturation conditions. The physical state of microparticles was also investigated. The formulation stability was evaluated over a 3-month period in long-term and accelerated conditions. The presence of amorphous NIF within freshly prepared microparticles was attributed to interactions between the drug and both polymers. NaPMM conferred to microparticles suitable mucoadhesive properties and significantly increased NIF dissolution rate in comparison to HPMC. Nevertheless, NIF apparent solubilities obtained by NaPMM microparticles were lower than those obtained by the HPMC set. After 3-month storage in the case of HPMC microparticles, NIF dissolution rate and supersaturation degree significantly decreased due to drug crystallization. As far as NaPMM microparticles are concerned, neither NIF dissolution rate nor apparent solubility significantly changed.     

Isolation and characterization of a novel gene induced by 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin in rat liver

The differential display technique was used to identify geneswhose expression was regulated by 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin(TCDD). Expression of a novel sequence was up-regulated in adose-dependent fashion in liver of Sprague-Dawley male ratsexposed to both chronic and acute treatment with TCDD, as measuredby densito-metry of Northern blot analyses (P < 0.01). Arapid amplification of cDNA ends (RACE) procedure was used toisolate a 1.8 kb cDNA from a rat liver cDNA preparation. Thiscloned cDNA, called 25-Dx, was sequenced and found to encodea peptide of 223 amino acids. In control rats, the 25-Dx genewas expressed at high levels in lung and liver. A hydrophobicdomain of 14 residues followed by a proline-rich domain, bothlocated in the N-terminal region, showed 71% homology with thetransmembrane domain of the precursor for the interleukin-6receptor and a conserved consensus sequence found in the cytokine/growthfactor/prolactin receptor superfamily respectively.     

Troponin-T levels in perinatally asphyxiated infants during the first 15 days of life

Aim: To measure serial cardiac troponin‐T, creatine kinase, creatine kinase‐MB, aspartate aminotransferase, alanine aminotransferase and lactate dehydrogenase levels in asphyxiated newborn infants during the first 15 d of life. Methods: Troponin‐T, creatine kinase, creatine kinase‐MB, aspartate aminotransferase, alanine aminotransferase and lactate dehydrogenase (LDH) concentrations were measured prospectively in blood samples obtained from 45 asphyxiated and 15 healthy term neonates within the first 2–4 h, third, seventh and 15th days. Results: Infants with severe asphyxia had significantly higher cardiac troponin‐T levels than grade I and II asphyxiated and healthy neonates within the first 2–4 h of life (0.34 ± 0.21 ag/ml vs 0.07 ± 0.03 ag/ml, 0.12 ± 0.07 ag/ml, 0.04 ± 0.02 ag/ml, respectively). Troponin‐T levels remained high on days 3 and 7 in severely asphyxiated neonates. The creatinine kinase‐MB levels were significantly higher in grade II and III asphyxiated neonates than grade I asphyxiated and healthy neonates within the first 2–4 h. No difference was found in creatinine kinase‐MB on day 3. There was cardiac involvement in 12 (80%) newborns of group III on B mode echocardiographic images on day 1. However, no echocardigraphic pathology was found in the seventh‐ and 15th‐day echocardiographic analysis in any groups. Conclusion: Our results suggest that asphyxia‐related cardiac changes were significant but reversible in severely asphyxiated neonates, and troponin T is a good determinant of the degree of injury to the heart within the first week of life. Cardiac troponin T also has a wider diagnostic frame than other diagnostic markers of myocardial damage.