Glass science behind lithium silicate glass-ceramics.

OBJECTIVES: Lithium silicate-based glass ceramics have evolved as a paramount restorative material in restorative and prosthetic dentistry, exhibiting outstanding esthetic and mechanical performance. Along with subtractive machining techniques, this material class has conquered the market and satisfied the patients' needs for a long-lasting, excellent, and metal-free alternative for single tooth replacements and even smaller bridgework. Despite the popularity, not much is known about the material chemistry, microstructure and terminal behaviour. METHODS: This article combines a set of own experimental data with extensive review of data from literature and other resources. Starting at manufacturer claims on unique selling propositions, properties, and microstructural features, the aim is to validate those claims, based on glass science. Deep knowledge is mandatory for understanding the microstructure evolution during the glass ceramic process. RESULTS: Fundamental glass characteristics have been addressed, leading to formation of time-temperature-transformation (TTT) diagrams, which are the basis for kinetic description of the glass ceramic process. Nucleation and crystallization kinetics are outlined in this contribution as well as analytical methods to describe the crystalline fraction and composition qualitatively and quantitatively. In relation to microstructure, the mechanical performance of lithium silicate-based glass ceramics has been investigated with focus on fracture strength versus fracture toughness as relevant clinical predictors. CONCLUSION: Fracture toughness has been found to be a stronger link to initially outlined manufacturer claims, and to more precisely match ISO recommendations for clinical indications.

Prefrontal and Hippocampal Parvalbumin Interneurons in Animal Models for Schizophrenia: A Systematic Review and Meta-analysis.

BACKGROUND: Consistent with postmortem findings in patients, most animal models for schizophrenia (SCZ) present abnormal levels of parvalbumin (PV), a marker of fast-spiking GABAergic interneurons, in the prefrontal cortex (PFC) and hippocampus (HIP). However, there are discrepancies in the literature. PV reductions lead to a functional loss of PV interneurons, which is proposed to underly SCZ symptoms. Given its complex etiology, different categories of animal models have been developed to study SCZ, which may distinctly impact PV levels in rodent brain areas. STUDY DESIGN: We performed a quantitative meta-analysis on PV-positive cell number/density and expression levels in the PFC and HIP of animal models for SCZ based on pharmacological, neurodevelopmental, and genetic manipulations. RESULTS: Our results confirmed that PV levels are significantly reduced in the PFC and HIP regardless of the animal model. By categorizing into subgroups, we found that all pharmacological models based on NMDA receptor antagonism decreased PV-positive cell number/density or PV expression levels in both brain areas examined. In neurodevelopmental models, abnormal PV levels were confirmed in both brain areas in maternal immune activation models and HIP of the methylazoxymethanol acetate model. In genetic models, negative effects were found in neuregulin 1 and ERBB4 mutant mice in both brain regions and the PFC of dysbindin mutant mice. Regarding sex differences, male rodents exhibited PV reductions in both brain regions only in pharmacological models, while few studies have been conducted in females. CONCLUSION: Overall, our findings support deficits in prefrontal and hippocampal PV interneurons in animal models for SCZ.

Sex-dependent differences in the anxiolytic-like effect of cannabidiol in the elevated plus-maze.

RATIONALE: Cannabidiol (CBD), the major non-psychoactive constituent of cannabis, has therapeutic potential for the treatment of anxiety. Most preclinical studies investigate only acute effects of CBD and only in males, yet the drug is most likely to be used over a sustained period in clinical practice. OBJECTIVES: The objectives of this study were to investigate the anxiolytic-like effect of CBD in female rats compared to males and to determine whether the responsiveness of females was influenced by the stage of the estrous cycle. METHODS: We carried out experiments to compare the effect of CBD in male and female rats in the elevated plus maze (EPM) in response to acute and short-term (4 days) administration through a complete cycle in females. RESULTS: Male and female rats behaved in a similar manner in the EPM, but females in the late diestrus (LD) phase exhibited more anxiety-like behavior than at other stages, the difference reaching statistical significance compared to proestrus stages. CBD produced anxiolytic-like effects in both sexes, but female rats were responsive only in LD and 10-fold lower dose than males. After sub-chronic (4 days) treatment, responsiveness to CBD was maintained in females in LD, but females in proestrus remained unresponsive to CBD treatment. CONCLUSIONS: We suggest that there are sex differences in the anxiolytic-like effects of CBD in rats that reflect different underlying mechanisms: based on literature data, gonadal hormone status linked to GABAA receptor expression in females, and 5-HT1A receptor activation in males.

The antinociceptive effect of anterior pretectal nucleus stimulation is mediated by distinct neurotransmitter mechanisms in descending pain pathways.

Electrical stimulation of the anterior pretectal nucleus (APtN) activates two descending pain inhibitory pathways. One of these pathways relays in the ipsilateral lateral paragigantocellular nucleus (LPGi), whereas the other pathway relays in the contralateral pedunculopontine tegmental nucleus (PPTg). Antinociceptive effect of APtN stimulation has been seen in various pain models in the rodents. Similarly, LPGi or PPTg stimulation results in higher pain thresholds. Descending antinociceptive pathways activated by electrical APtN stimulation have been elucidated, but the underlying neurotransmitter mechanisms involved have not been clarified yet. This study investigates the role that endogenous signaling plays in the ipsilateral LPGi or contralateral PPTg after the APtN is stimulated in the tail-flick test. First, we submitted rats to excitotoxic injection of N-methyl-d-aspartate (NMDA) into the contralateral PPTg. Then, we examined whether blockage of NMDA (AP-7), serotonergic (methysergide), or opioid (naloxone) receptors in the ipsilateral LPGi is required for APtN stimulation-evoked analgesia (SEA). Likewise, we examined the effects of antagonists of NMDA, serotonergic, or cholinergic nicotinic (mecamylamine) receptors on the contralateral PPTg in ipsilateral LPGi-lesioned rats. Our results confirmed that APtN stimulation activates two pain inhibitory pathways and showed that endogenous opioid signaling in the ipsilateral LPGi appears to be necessary for APtN SEA and for endogenous NMDA, serotoninergic, and nicotinergic signaling in the contralateral PPTg.

Angiotensin AT1 receptors modulate the anxiogenic effects of angiotensin (5-8) injected into the rat ventrolateral periaqueductal gray.

Losartan and PD 123,319 are non-peptide angiotensin (Ang) receptor antagonists for the AT1 and AT2 subtypes of Ang II receptors, respectively. The tetrapeptide Ang (5-8) is the smallest Ang-peptide that elicits anxiogenic effects on unconditioned and conditioned experimental models upon injection into the ventrolateral column of the periaqueductal gray (vlPAG), and Ang (5-8) can be synthesized (from Ang II or Ang III) and inactivated in this mesencephalic structure. The vlPAG is also known to play a central role in mechanisms of fear and anxiety. We therefore utilized male Wistar rats to examine the effects of losartan and PD 123,319 injections, selective antagonists of the AT1 and AT2 receptors, respectively, into the vlPAG in the elevated plus-maze, a classic rat model of anxiety, and against the anxiogenic effect of Ang (5-8) (0.4 nmol/0.25µL) upon injection into the same region. The anxiolytic profile was dependent on the dose of intra-vlPAG losartan, whereas no effects on experimental anxiety were observed in the plus-maze following PD 123,319 injection. The anxiogenic effect of Ang (5-8) injection into the vlPAG remained unchanged in the PD 123,319-pretreated rats, but the effect did not occur in losartan-pretreated rats. The results led us to suggest that the anxiogenic effect of Ang (5-8) injection into the vlPAG may depend on the local activation of AT1, but not AT2 receptors. Activation of AT1 receptors in structures nearby vlPAG may be tonically involved in fear and experimental anxiety.

Cannabidiol Is a Potential Therapeutic for the Affective-Motivational Dimension of Incision Pain in Rats.

Background: Pain involves different brain regions and is critically determined by emotional processing. Among other areas, the rostral anterior cingulate cortex (rACC) is implicated in the processing of affective pain. Drugs that interfere with the endocannabinoid system are alternatives for the management of clinical pain. Cannabidiol (CBD), a phytocannabinoid found in Cannabis sativa, has been utilized in preclinical and clinical studies for the treatment of pain. Herein, we evaluate the effects of CBD, injected either systemically or locally into the rACC, on mechanical allodynia in a postoperative pain model and on the negative reinforcement produced by relief of spontaneous incision pain. Additionally, we explored whether CBD underlies the reward of pain relief after systemic or rACC injection. Methods and Results: Male Wistar rats were submitted to a model of incision pain. All rats had mechanical allodynia, which was less intense after intraperitoneal CBD (3 and 10 mg/kg). Conditioned place preference (CPP) paradigm was used to assess negative reinforcement. Intraperitoneal CBD (1 and 3 mg/kg) inverted the CPP produced by peripheral nerve block even at doses that do not change mechanical allodynia. CBD (10 to 40 nmol/0.25 µL) injected into the rACC reduced mechanical allodynia in a dose-dependent manner. CBD (5 nmol/0.25 µL) did not change mechanical allodynia, but reduced peripheral nerve block-induced CPP, and the higher doses inverted the CPP. Additionally, CBD injected systemically or into the rACC at doses that did not change the incision pain evoked by mechanical stimulation significantly produced CPP by itself. Therefore, a non-rewarding dose of CBD in sham-incised rats becomes rewarding in incised rats, presumably because of pain relief or reduction of pain aversiveness. Conclusion: The study provides evidence that CBD influences different dimensions of the response of rats to a surgical incision, and the results establish the rACC as a brain area from which CBD evokes antinociceptive effects in a manner similar to the systemic administration of CBD. In addition, the study gives further support to the notion that the sensorial and affective dimensions of pain may be differentially modulated by CBD.