Effect of Aqueous and Ethanolic Extracts of Nigella sativa Seeds on Milk Production in Rats

Nigella sativa L. is used as a galactagogue in traditional medicine. Hence, the effects of aqueous and ethanolic extracts of N. sativa seeds on milk production in rats were evaluated. The measurement of milk production was by measuring pup weight during suckling period. The intraperitoneal LD₅₀ values of aqueous and ethanolic extracts of N. sativa were 4.23 and 4.9 g/kg, respectively. The aqueous (0.5 g/kg) and ethanolic extracts (1 g/kg) increased milk production significantly (p < 0.001), producing about 31.3% and 37.6% more milk than control, respectively. During the study period, the pups gained weight with the aqueous (0.5 g/kg, p < 0.01) and ethanolic extracts (1 g/kg, p < 0.05). It is concluded that aqueous and ethanolic extracts of N. sativa can stimulate milk production in rats.     

Congenital Insensitivity to Pain with Anhidrosis Presenting with Palmoplantar Keratoderma

Abstract: Congenital insensitivity to pain with anhidrosis (CIPA) is a rare autosomal‐recessive disease caused by mutations in the NTRK1 gene. The disease is characterized by insensitivity to pain and absence of thermal perception. Herein a 6‐year‐old boy is presented with a large ulcer on the sole of his right foot and a thick, hyperkeratotic appearance of his palms and soles; there was also a medical history of hyperthermia, anhidrosis, recurrent bone fractures, osteomyelitis, injuries, mental retardation, dry and exfoliative skin, insensitivity to pain, and lack of thermal sensation. Genetic studies revealed a homozygote mutation in the NTRK1 gene. Although the patient initially presented with palmoplantar keratoderma, genetic studies confirmed the diagnosis of CIPA.     

Adult-onset epilepsy and history of childhood febrile seizures: a retrospective study

BACKGROUND: Children with febrile seizures (FS) are at higher risk of developing epilepsy. There is robust literature on epilepsy with onset in childhood following FS but very little on the same issue in adults. AIMS: We intended to assess the association between adult-onset epilepsy and history of childhood FS. SETTINGS: The neurology clinic of a university hospital. DESIGN: A retrospective study. MATERIALS AND METHODS: Records of 101 consecutive adults (>14 years old) who were referred to our hospital with adult-onset seizures were reviewed and the patients and their families were interviewed to assess the medical history. STATISTICAL ANALYSIS: Chi-square test and Mantel-Haenszel method. RESULTS: Of the 101 patients, 9 were excluded for reasons of bacterial meningitis, recent head trauma, brain tumor, tricyclic antidepressants' overdose and missing reliable data of the childhood FS event. Thirty-one (33.7%) of the remaining 92 patients had history of FS in the childhood (71% men). Localization-related epilepsies were significantly associated with history of FS [Odds ratio: 3.29; (95% CI, 1.30-8.06)] ( (2)= 5.49, df = 1, P=0.012) when compared to other epilepsies and epilepsy syndromes. An initial unprovoked simple partial seizure was also significantly associated with a positive history of FS [Odds ratio: 8.05; (95% CI 2.88-22.45)] ( (2)= 15.86, df = 1, P< 0.001). CONCLUSIONS: Localization-related epilepsies and partial seizures seem to be associated with a history of FS in childhood. This warrants more investigation to understand the mechanism as well as a possible pathology common in both localization-related epilepsies and FS in the affected probands.     

In vitro and in vivo study of 99mTc-MIBI encapsulated in PEG-liposomes: a promising radiotracer for tumour imaging

Encapsulation of technetium-99m sestamibi ((99m)Tc-MIBI) in polyethyleneglycol-liposomes ((99m)Tc-MIBI-PEG-liposomes) could extend the duration of its circulation in blood and alter its biodistribution, enabling its concentration in tumours to be increased. An original method to encapsulate (99m)Tc-MIBI in PEG-liposomes is described. The (99m)Tc-MIBI-PEG-liposomes were compared with free (99m)Tc-MIBI with respect to (a) tumour availability (b) ability to distinguish between chemotherapy-sensitive and -resistant cells and (c) uptake ratio in tumour imaging. PEG-liposomal systems composed of distearoylphosphatidylcholine/cholesterol/PEG(2000)-distearoyl phosphatidylethanolamine and lissamine-rhodamine B-labelled liposomes were used. The encapsulation of (99m)Tc-MIBI in liposomes was achieved using the K(+) diffusion potential method. We compared the uptake of free versus encapsulated (99m)Tc-MIBI by sensitive and resistant erythroleukaemia (K562) and breast tumour (MCF-7ras) cells. To assess the internalisation of these liposomes into cells, rhodamine B-labelled PEG-liposomes were used and visualised by fluorescence microscopy. Biodistribution and imaging characteristics of encapsulated and free radiotracer were determined in rats and tumour-bearing nude mice. The efficiency of (99m)Tc-MIBI encapsulation in PEG-liposomes was 50+/-5%. Use of (99m)Tc-MIBI-PEG-liposomes did not impair the ability of this tracer to distinguish between chemotherapy-sensitive and -resistant tumour cells; the percentage of radioactivity accumulated in the sensitive K562 cells was 1.24+/-0.04%, as compared with 0.41+/-0.04% in the resistant K562 cells. One hour post injection in rats, PEG-liposomes showed a ten times higher activity in blood than free (99m)Tc-MIBI, whereas activity of free (99m)Tc-MIBI in kidneys and bladder was markedly higher than that of encapsulated (99m)Tc-MIBI, indicating faster clearance of the free radiotracer. In the (MCF7-ras)-bearing nude mice, PEG-liposome uptake in tumour was two times that of free (99m)Tc-MIBI. Summarising, the (99m)Tc-MIBI-PEG-liposomes demonstrated a longer blood circulation time, enabled distinction between chemotherapy-sensitive and -resistant cells and improved tumour to background contrast in in vivo imaging. (99m)Tc-MIBI-PEG-liposomes therefore show promising potential for tumour imaging.     

Acute Toxicity Evaluation of Glycosylated Gd<Superscript>3+</Superscript>-Based Silica Nanoprobe

Purpose

Early stage diseases diagnosed using magnetic resonance imaging (MRI) techniques is of high global interest as a potent noninvasive modality. MRI contrast agents are improved through modifications in structural and physicochemical properties of the applied nanoprobes. But, the potential toxic effects of nanoprobes upon exposure to biological systems are still a major concern.

Procedure

In this study, the acute toxicity of glycosylated Gd³⁺-based silica mesoporous nanospheres (GSNs) as a MRI contrast agent was evaluated in Balb/c mice. In order to evaluate in vivo toxicity of GSN, preclinical studies, daily weight monitoring, hematological/blood chemistry tests, and histological assessment were conducted. Magnetic resonance relaxivities of GSN was determined using a MRI scanner.

Results

The obtained results suggest that in vivo toxicity of GSN was mostly influenced by nanoparticle surface area, functionality, and nanoparticle zeta potential. The maximum tolerated dose (MTD) increased in the following order: mesoporous silica nanospheres (MSNs) at 1 mg/mice < GSN (aspect ratio 1, 2, 8) at 40 mg/mice. The results also indicate GSN, one of the best cell imaging contrast agent, which does not show any significant toxicity on multiple vital organs following injection of 20 mg/mice, while a significant T₁-weighted enhancement was observed in whole body of a Balb/c mice 15 min postinjection of (5 μmol/kg) of body weight of GSN.

Conclusions

These results shed light on the functionality of MSNs to minimize in vivo toxicity. Also, glyconanoprobe can be beneficially used for nanomedicine and cellular imaging applications without any significant toxicity.

     

Adolescent Dopamine Neurons Represent Reward Differently during Action and State Guided Learning

Neuronal underpinning of learning cause-and-effect associations in the adolescent brain remains poorly understood. Two fundamental forms of associative learning are Pavlovian (classical) conditioning, where a stimulus is followed by an outcome, and operant (instrumental) conditioning, where outcome is contingent on action execution. Both forms of learning, when associated with a rewarding outcome, rely on midbrain dopamine neurons in the ventral tegmental area (VTA) and substantia nigra (SN). We find that, in adolescent male rats, reward-guided associative learning is encoded differently by midbrain dopamine neurons in each conditioning paradigm. Whereas simultaneously recorded VTA and SN adult neurons have a similar phasic response to reward delivery during both forms of conditioning, adolescent neurons display a muted reward response during operant but a profoundly larger reward response during Pavlovian conditioning. These results suggest that adolescent neurons assign a different value to reward when it is not gated by action. The learning rate of adolescents and adults during both forms of conditioning was similar, supporting the notion that differences in reward response in each paradigm may be because of differences in motivation and independent of state versus action value learning. Static characteristics of dopamine neurons, such as dopamine cell number and size, were similar in the VTA and SN of both ages, but there were age-related differences in stimulated dopamine release and correlated spike activity, suggesting that differences in reward responsiveness by adolescent dopamine neurons are not because of differences in intrinsic properties of these neurons but engagement of different dopaminergic networks.SIGNIFICANCE STATEMENT Reckless behavior and impulsive decision-making by adolescents suggest that motivated behavioral states are encoded differently by the adolescent brain. Motivated behavior, which is dependent on the function of the dopamine system, follows learning of cause-and-effect associations in the environment. We find that dopamine neurons in adolescents encode reward differently depending on the cause-and-effect relationship of the means to receive that reward. Compared with adults, reward contingent on action led to a muted response, whereas reward that followed a cue but was not gated by action produced an augmented phasic response. These data demonstrate an age-related difference in dopamine neuron response to reward that is not uniform and is guided by processes that differentiate between state and action values.