Effects of cannabis and its components on the retina: a systematic review

Abstract

Purpose: Cannabis is the most prevalent drug in the world and its consumption is growing. Cannabinoid receptors are present in the human central nervous system. Recent studies show evidence of the effects of cannabinoids on the retina, and synthesising the results of these studies may be relevant for ophthalmologists. Thus, this review adopts standardised, systematic review methodology to investigate the effects of exposure to cannabis and components on the retina.

Methods: We searched five online databases for the combined terms for outcome (“retina”) and exposure (“cannabis”). Eligibility of studies were conducted by two independent reviewers, and risk of bias was assessed.

Results: We retrieved 495 studies, screened 229 studies, assessed 52 studies for eligibility, and included 16 studies for qualitative analysis. The cannabinoids most frequently investigated were delta-9-tetrahydrocannabinol (THC), abnormal cannabidiol, synthetic cannabinoid, and cannabidiol (CDB). The outcomes most studied were neuroretinal dysfunction, followed by vascular effects. The studies also included investigation of neuroprotective and anti-inflammatory effects and teratogenic effects.

Conclusions: This review suggests that cannabinoids may have an important role in retinal processing and function.     

AD80, a multikinase inhibitor,exhibits antineoplastic effects in acute leukemia cellular models targeting the PI3K/STMN1 axis

Investigational New Drugs - Despite the great advances in the understanding of the molecular basis of acute leukemia, very little of this knowledge has been translated into new therapies. Stathmin...     

Caffeine and 35% carbon dioxide challenge tests in panic disorder

Our aim was to compare the demographic and clinical features of panic disorder (PD) patients with agoraphobia-DSM-IV-who had a panic attack after both an oral caffeine and the 35% carbon dioxide (CO2) challenge tests (responsive group) and compare them with PD patients who did not have a panic attack after both tests (non-responsive group). We examined 83 PD patients submitted to a 35% CO2 test and to an oral caffeine (480 mg) intake within 1 week interval. A panic attack was induced in 51 (61.4%) patients during the CO2 test (chi2=31.67, df=1, p<0.001) and in 38 (45.8%) patients during the caffeine test (chi2=18.28, df=1, p=0.023). All patients who had a panic attack during the caffeine test also had a panic attack during the CO2 test (n=38)-responsive group. The responsive had more (chi2=24.55, df=1, p=0.008) respiratory PD subtype, disorder started earlier (Mann-Whitney, p<0.001) had a higher familial prevalence of PD (chi2=20.34, df=1, p=0.019), less previous alcohol abuse (chi2=23.42, df=1, p<0.001), and had more previous depressive episodes (chi2=27.35, df=1, p<0.001). Our data suggest that there is an association between respiratory PD subtype and hyperreactivity to challenge tests: CO2 and oral caffeine.     

Rotundifolone-induced relaxation is mediated by BK(Ca) channel activation and Ca(v) channel inactivation

Rotundifolone is the major constituent of the essential oil of Mentha x villosa Hudson. In preliminary studies, rotundifolone induced significant hypotensive, bradycardic and vasorelaxant effects in rats. Thus, to gain more insight into the pharmacology of rotundifolone, the aim of this study was to characterize the molecular mechanism of action involved in relaxation produced by rotundifolone. The relaxant effect was investigated in rat superior mesenteric arteries by using isometric tension measurements and whole-cell patch-clamp techniques. Rotundifolone relaxed phenylephrine-induced contractions in a concentration-dependent manner. Pre-treatment with KCl (20 mM), charybdotoxin (10(-7) M) or tetraethylammonium (TEA 10(-3) or 3 × 10(-3) M) significantly attenuated the relaxation effect induced by rotundifolone. Additionally, whole-cell patch-clamp recordings were made in mesenteric smooth muscle cells and showed that rotundifolone significantly increased K(+) currents, and this effect was abolished by TEA (10(-3) M), suggesting the participation of BK(Ca) channels. Furthermore, rotundifolone inhibited the vasoconstriction induced by CaCl(2) in depolarizing nominally Ca(2+) -free medium and antagonized the contractions elicited by an L-type Ca(2+) channel agonist, S(-)-Bay K 8644 (2 × 10(-7) M), indicating that the vasodilatation involved inhibition of Ca(2+) influx through L-type voltage-dependent calcium channels (Ca(v) type-L). Additionally, rotundifolone inhibited L-type Ca(2+) currents (I(Ca) L), affecting the voltage-dependent activation of I(Ca) L and steady-state inactivation. Our findings suggest that rotundifolone induces vasodilatation through two distinct but complementary mechanisms that clearly depend on the concentration range used. Rotundifolone elicits an increase in the current density of BK(Ca) channels and causes a shift in the steady-state inactivation relationship for Ca(v) type-L towards more hyperpolarized membrane potentials.     

1-(7-Chloroquinolin-4-yl)-2-[(1H-pyrrol-2-yl)methylene]hydrazine: a potent compound against cancer

Heteroaromatic derivatives (3a–f) have been synthesized and evaluated for their activity against four cancer cell lines. Among the studied compounds, 1-(7-Chloroquinolin-4-yl)-2-[(1H-pyrrol-2-yl)methylene]hydrazine (3e) exhibited an excellent cytotoxic activity against the referred lines, and especially on melanoma cells (MDAMB-435). In this case, compound 3e is four times more active than the standard substance Doxorubicin. Together with other results from our group, 7-chloro-4-quinolinylhydrazones derived from chloroquine could be considered a relevant finding toward the rational design of new leads for antitumor compounds.     

A rationale method for evaluating unscrewing torque values of prosthetic screws in dental implants

Objectives

Previous studies that evaluated the torque needed for removing dental implant screws have not considered the manner of transfer of the occlusal loads in clinical settings. Instead, the torque used for removal was applied directly to the screw, and most of them omitted the possibility that the hexagon could limit the action of the occlusal load in the loosening of the screws. The present study proposes a method for evaluating the screw removal torque in an anti-rotational device independent way, creating an unscrewing load transfer to the entire assembly, not only to the screw.

Material and methods

Twenty hexagonal abutments without the hexagon in their bases were fixed with a screw to 20 dental implants. They were divided into two groups: Group 1 used titanium screws and Group 2 used titanium screws covered with a solid lubricant. A torque of 32 Ncm was applied to the screw and then a custom-made wrench was used for rotating the abutment counterclockwise, to loosen the screw. A digital torque meter recorded the torque required to loosen the abutment.

Results

There was a significant difference between the means of Group 1 (38.62±6.43 Ncm) and Group 2 (48.47±5.04 Ncm), with p=0.001.

Conclusion

This methodology was effective in comparing unscrewing torque values of the implant-abutment junction even with a limited sample size. It confirmed a previously shown significant difference between two types of screws.