The effects of N-Acetylcysteine on frontostriatal resting-state functional connectivity, withdrawal symptoms and smoking abstinence: A double-blind, placebo-controlled fMRI pilot study.

BACKGROUND: Chronic exposure to drugs of abuse disrupts frontostriatal glutamate transmission, which in turn meditates drug seeking. In animal models, N-Acetylcysteine normalizes dysregulated frontostriatal glutamatergic neurotransmission and prevents reinstated drug seeking; however, the effects of N-Acetylcysteine on human frontostriatal circuitry function and maintaining smoking abstinence is unknown. Thus, the current study tested the hypothesis that N-Acetylcysteine would be associated with stronger frontostriatal resting-state functional connectivity (rsFC), attenuated nicotine withdrawal and would help smokers to maintain abstinence over the study period. METHODS: The present study examined the effects of N-Acetylcysteine on frontostriatal rsFC, nicotine-withdrawal symptoms and maintaining abstinence. Healthy adult, non-treatment seeking smokers (N=16; mean (SD) age 36.5±11.9; cigs/day 15.8±6.1; years/smoking 15.7±8.9) were randomized to a double-blind course of 2400mg N-Acetylcysteine (1200mg b.i.d.) or placebo over the course of 3½ days of monetary-incentivized smoking abstinence. On each abstinent day, measures of mood and craving were collected and participants attended a lab visit in order to assess smoking (i.e., expired-air carbon monoxide [CO]). On day 4, participants underwent fMRI scanning. RESULTS: As compared to placebo (n=8), smokers in the N-Acetylcysteine group (n=8) maintained abstinence, reported less craving and higher positive affect (all p's<.01), and concomitantly exhibited stronger rsFC between ventral striatal nodes, medial prefrontal cortex and precuneus-key default mode network nodes, and the cerebellum [p<.025; FWE]). CONCLUSIONS: Taken together, these findings suggest that N-Acetylcysteine may positively affect dysregulated corticostriatal connectivity, help to restructure reward processing, and help to maintain abstinence immediately following a quit attempt.

Can total urinary protein measurements predict microalbuminuria?

We re-addressed the question of whether routine total urinary protein determinations can be used to predict the presence of microalbuminuria by studying 61 patients who attended a diabetic clinic and tested negative or had one positive protein by dipstick. Total urinary protein was measured by the Biorad dye-binding method in undialyzed urine (UND), in dialyzed urine (DIAL), and in dialyzed urine in which albumin and globulins were separated, measured separately with albumin and globulin standards and the results added together to obtain total urinary protein (A + G). The results were compared with albumin measurements obtained by radioimmunoassay (RIA). Compared to DIAL, urinary protein measurements were 43% higher with A + G and 22% higher with UND. Microalbuminuria correlated moderately with UND (r =0.81) and better with the other methods (r=0.87 for DIAL, r=0.91 for A + G). None of the methods predicted microalbuminuria reliably. Taking a protein-to-creatinine ratio of 0.15 and an albumin-to-creatinine ratio of 0.03 as upper limits of normal, we found that UND had a 72% positive predictive value (28% false positives) and 85 % negative predictive value (15% false negatives). DIAL had 90% positive predictive value (10% false positives) and 78% negative predictive value (22% false negatives). A + G had 65% positive predictive value (35% false positives) but 91% negative predictive value (9% false negatives). A + G, which uses the correct standards, would be the most suitable method for screening, having the least number of false negatives, but has more false positives because it is more sensitive. In practice, most routine chemical laboratories find it expedient to use only UND, but physicians interpreting the results of this method should be aware of its limitations.

Mesangial lupus nephritis with associated nephrotic syndrome.

Patients with mesangial proliferative lupus glomerulonephritis (World Health Organization class II) are generally believed to have only mild to moderate proteinuria and normal renal function. However, there have been several reports of patients with mesangial lupus with nephrotic-range proteinuria. In this report, we present two additional cases and review the literature. Of seven reported cases, persistent nephrotic syndrome was observed in four, morphologic transformation occurred in three, and all but one presented with varying degrees of azotemia. These cases reinforce the concept that in systemic lupus erythematosus, laboratory findings may not correlate well with the underlying glomerular lesion, and therefore, the renal biopsy is an essential clinical tool in the approach to lupus nephritis.