Do your kidneys ever adjust???

what the kidneys do

An organ involved with the elimination of water and waste products from the body. In vertebrates the kidneys are paired organs located close to the spine dorsally in the body cavity. They consist of a number of smaller functional units called urinary tubules or nephrons. The nephrons open to large ducts, the collecting ducts, which open into a ureter. The two ureters run backward to open into the cloaca or into a urinary bladder. In mammals, the kidneys are bean-shaped and found between the thorax and the pelvis. The number, structure, and function of the nephrons vary with evolution and, in certain significant ways, with the adaptation of the animals to their various habitats.
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the world of the body
The kidneys are situated on each side of the vertebral column, at the level of the last (twelfth) rib. Each kidney is about 12 cm long and weighs about 150 g — about the size of a fist. Despite their small size, the two kidneys receive an enormous blood flow — about 1.2 litres/min in an adult — which is a quarter of the total output of the heart (5 litres/min).

One of the main functions of the kidneys is the removal from the body (excretion) of waste products such as urea, uric acid, and creatinine. However, the kidneys' role is not merely excretion. They are also regulatory organs, controlling the volume and the composition of the body fluids and maintaining the correct osmolality, ion concentrations, and acid-base status of the body.


Each kidney is bean-shaped, with a slit opening — termed the hilus — through which pass the renal artery and vein, the renal nerves and lymphatics, and the ureter, which connects the kidney to the bladder (Fig. 1). A tough connective tissue capsule covers the outer layer of the kidney, the cortex. The deeper part of the kidney, the medulla, consists of a number (6-18) of conical pyramids, the tips of which (papillae) project into the funnel-shaped urine collectors — the renal calyxes (calices) — which merge to form the funnel-shaped upper end of the ureter — the renal pelvis. (Renal, pertaining to the kidney, from its Latin name, ren.)

The nephron is the functional unit of the kidney. (Nephros is the Greek for kidney.) Each kidney has about one million nephrons, and the total length of the nephrons in the body is about 100 miles!

The nephron begins as a Bowman's capsule — the blind end of the nephron — invaginated by a knot of capillaries, the glomerulus (glomerular capillaries). A Bowman's capsule and its glomerular capillaries are together termed a renal corpuscle. Sir William Bowman, British surgeon and histologist, described this in 1842.

The rest of the nephron consists of the proximal convoluted tubule, proximal straight tubule, loop of Henle, and distal convoluted tubule. The distal tubules join to form collecting tubules which in turn join to form collecting ducts, which open at the tip of the renal papilla (Fig. 2).

The Bowman's capsules, proximal tubules, and distal tubules are situated in the renal cortex, whereas the loops of Henle and the collecting ducts extend down through the medulla.




http://www.answers.com/kidneys?cat=h...&ver=2.3.0.609

Tylenol And Kidney Problems -
Tylenol and Aspirin Increases Risk of Kidney Failure
An article in the December 19, 2001 online issue of WebMD reporting on an article from the December 20, 2001 New England Journal of Medicine reports that two of the most common over the counter drugs can have serious effects. The study was conducted in Sweden by interviewing 1924 subjects half of who had been recently diagnosed with renal (kidney) failure. In the half that had the renal failure the usage of Aspirin and Tylenol was 37 percent and 25 percent, respectively. In the control group, the usage of Aspirin and Tylenol was considerably lower with the rates only being 19 percent and 12 percent, respectively. These results clearly showed a higher rate of long-term usage of these drugs in the patients who eventually suffered renal failure.

Michael Fored, MD, author of the study and a kidney specialist at the Karolinska Institute in Stockholm, Sweden stated, "What we have seen is that there is an association between acetaminophen [the generic name for Tylenol] and aspirin and chronic [kidney] failure. Our results are consistent with the existence of exacerbating effects of acetaminophen and aspirin on chronic renal failure."

The WebMD story stated that taking either of the two drugs increased risk of kidney failure for people with kidney disease. The article further pointed out that taking just one of the drugs increased this risk 2.5-fold while taking more of each drug over the course of a lifetime, greatly increased the risk. Cumulative (lifetime) risk increased faster with Tylenol than with aspirin. A lifetime dose of at least 500 grams increased risk of kidney failure 3.3-fold. "This is not that high a dose," Fored says. "For the usual 500 mg pill that is 1,000 tablets. That is three tablets a day for a year. It is not that high a dose for a person with chronic pain."

The very next article published in the same December 20, 2001 issue of the New England Journal of Medicine reports on a study that shows that taking ibuprofen (Advil or Motrin) almost totally wipes out any positive heart effects that taking aspirin was hoping to cause.

In this report by Dr. Muredach Reilly, a University of Pennsylvania cardiologist who took part in the 30-patient study, he noted that when patients took a single dose of ibuprofen beforehand, aspirin lost 98 percent of its blood-thinning power. When aspirin was taken first, three daily doses of ibuprofen sapped aspirin of 90 percent of its benefit. He concluded, “It would not do you a lot of good to take one medication only to have another wipe out its effects.”

http://www.chiropracticresearch.org/..._increases.htm

read some of these articles -

http://www.chiropracticresearch.org/

Rick, what problem are your having?? I wonder if Zandopa involves heating the velvet beans.....

Might be relevant:

English Title: Heating raw velvet beans (Mucuna pruriens) reverses some anti-nutritional effects on organ growth, blood chemistry, and organ histology in growing chickens.
Personal Authors: Carew, L. B., Hardy, D., Weis, J., Alster, F., Mischler, S. A., Gernat, A., Zakrzewska, E. I.


Abstract:

Velvet beans (Mucuna pruriens) represent an interesting food and feed commodity because of the presence of harmful, but also potentially beneficial components that have been poorly studied. We developed a joint research project between the University of Vermont in the USA and the Escuela Agricola Panamericana (Zamorano) in Honduras to study the role of velvet beans (VB) in chicken nutrition and to determine methods for improving their usefulness and safety.

The results of these studies, using the chicken as a research model, have application to all monogastric animals including humans with whom such research cannot be done. The two experiments described herein measured the effects of raw VB on the anatomy and blood chemistry of the chick, and the role that heating the velvet beans has on reversing any harmful effects inherent in the beans themselves.

Consumption of unprocessed, raw velvet beans by broiler chickens reduced body weight gain. Weights (relative to body weight) of the pancreas, gizzard, and proventriculus (stomach), as well as lengths of the small and large intestines, and ceca, increased in birds fed raw VB.

Most of these changes were partially or wholly reversed by dry heating (i.e. toasting) the beans. It is likely that the effects of heating reflect, to some degree, partial destruction of anti-nutritional factors. Effects of VB on liver and heart weights were inconclusive. Significant changes were also found in blood components.

Plasma creatinine was reduced to a similar degree in chicks fed both raw and heated VB, and most likely reflects changes in muscle mass or metabolism concurrent with feeding either form of VB. Plasma cholesterol levels were also consistently reduced in chicks fed raw VB compared to their pair-fed controls. These findings agree with our previous results and work done by others in a rat model. However, heating VB caused an even further reduction in plasma cholesterol. This may indicate the presence of a cholesterol-lowering substance in VB.

Some anti-nutritional factors in VB may be heat-resistant and may explain such effects, although the effect of dietary fiber cannot be ruled out.

Alanine aminotransferase was elevated in chicks fed both raw and heated VB compared to their pair-fed controls, and this is often an indication of liver damage. Intake of raw VB had inconsistent effects on plasma thyroxine and triiodothyronine, and little effect on the plasma content of sodium, glucose and alkaline phosphatase.

The microanatomy of the pancreas, liver, small intestine and kidney was altered in chickens fed raw VB. Increases in pancreatic necrosis, hepatic cellular degeneration and thinning of the mucosal muscular layer of the small intestine appeared to be at least partially a consequence of the reduced growth rate, as shown by pair feeding comparisons, and not to the VB themselves.

However, kidney damage, as shown by invasion of blood into the renal tubules, was directly a result of feeding raw VB. Heating VB partially reversed this effect.

Heating VB also partially reversed the thinning of the intestinal musculature. It is concluded that the many anti-nutritional factors in VB affect diverse parameters in growing chickens. Such anti-nutritional/toxic effects of raw VB may have similar effects on other monogastric species, including humans. Heating VB can reduce some of these deleterious effects, and our results suggest that heating can be an important adjunct to other processing methods to improve the nutritional value of VB. For greater accuracy, however, standardized methods of processing and analyzing VB must be developed to reduce observed variability.

Publisher: Facultad de Medicina Veterinaria y Zootecnia, Universidad Autonoma de Yucatan

\http://www.cababstractsplus.org/goog...No=20043167771

Journal of Neurology Neurosurgery and Psychiatry 2004;75:1672-1677

Mucuna pruriens in Parkinson’s disease: a double blind clinical and pharmacological study

"Full blood count, and liver and renal function blood tests were taken at baseline and after completion of the study."

http://jnnp.bmj.com/cgi/content/full/75/12/1672

Safety and tolerability

Apart from one patient who dropped out due to shortlasting vomiting on 30 g mucuna, the other adverse events were: mild and shortlasting nausea occurring in two patients with LD/CD and in two patients with 30 g mucuna; mild gastric pain in one patient with LD/C; and mild dizziness in one patient each with LD/CD and 15 g mucuna. No clinically relevant changes in haematology or biochemistry parameters were observed.....

DISCUSSION:

Our study demonstrates that the seed powder formulation of M pruriens contains a considerable quantity of L-dopa which, at a dose of 30 g, is sufficient to consistently induce a sustained on-period in fluctuating PD patients with short duration L-dopa response. The quality of motor improvement was equivalent to that seen with synthetic LD/CD, but the onset of action, duration of effect, and pharmacokinetic profiles differed considerably.

The latency to clinical onset was significantly and markedly shorter with mucuna than with synthetic LD/CD. The duration of the on-period was significantly longer with 30 g mucuna than with LD/CD, with a mean difference of 37 min. The time from the beginning of a visible antiparkinsonian effect to returning to a full "off" was significantly longer with 30 g mucuna, providing an additional 46 min when patients were partially "on".

Compared to literature reports on dispersible L-dopa formulations, the latency to the onset of effect following mucuna in our study was within a similar range. However, the duration of on-time achieved with 30 g mucuna was considerably longer: the time patients spent in a full on-state was 204 min following 30 g mucuna, compared with 14819 and 97 min20 reported in two studies with dispersible L-dopa formulations.

These clinical findings were reflected in the pharmacokinetic profile of L-dopa concentrations, which showed a significantly higher peak plasma concentration with 30 g mucuna, occurring after a shorter latency Tmax. The difference in Tmax was significant with 15 g and only narrowly missed reaching significance with 30 g.

Peak L-dopa concentrations on mucuna were followed by a decline which was faster with 15 g mucuna but similar to LD/CD with 30 g mucuna, resulting in a significantly larger total AUC with 30 g mucuna.

These findings suggest that M pruriens formulations may actually have a higher bioavailability than standard L-dopa preparations. Although the latency to peak concentrations with LD/CD was rather long at 95.5 min, this is within the upper range of reported findings with standard L-dopa preparations.21,22 All reasonable and practical measures were taken to avoid dietary interferences. Drugs that could inhibit gastrointestinal absorption were excluded, and none of the patients had known malabsorption syndromes or other gastrointestinal conditions. However, all the patients had been on long term L-dopa therapy for many years prior to the study.

The most obvious differences between the mucuna preparation and the synthetic formulation used in this study were the administration of mucuna in the form of a suspension as opposed to a capsule, and the presence of a dopa decarboxylase inhibitor in the standard L-dopa preparation. Decarboxylase inhibitors mainly increase L-dopa plasma concentrations by blocking the peripheral degradation of L-dopa to dopamine, thus allowing more L-dopa to cross the blood–brain barrier. However, the gastrointestinal mucosa is a site for decarboxylation of oral L-dopa23 and decarboxylase inhibitors have been reported to enhance duodenal L-dopa absorption,24,25 presumably by inhibiting metabolic pathways such as aromatic dehydroxylation in the gut.22 Adding a decarboxylase inhibitor leads to considerably higher peak L-dopa concentrations.9,10,26 One study proposed a doubling of the bioavailability of oral L-dopa in the presence of a decarboxylase inhibitor, but this was based on findings with intravenously administered L-dopa.27 Studies investigating oral L-dopa invariably reported a reduction of exogenous L-dopa by 60–80%.10,11,13,28 The conversion factor of 1:5 chosen for the 30 g mucuna dose in relation to standard LD/CD (L-dopa reduction by 80%) is in the upper range of reported ratios. It is possible that the truly corresponding dose is slightly less than 30 g, but this does not seem sufficient to explain the large differences in pharmacokinetic and clinical findings.

The impact of decarboxylase inhibitors on latency to peak concentrations varies in the reported literature. This has been found to be either shorter,26 similar,10,12,29 or longer9 compared with L-dopa alone, and one study28 found a dose-dependent reduction in Tmax in the presence of CD. Although the delay to maximum plasma concentration of 95.5 min found in our study appears rather long, similar delays on standard release LD/decarboxylase inhibitor have been reported in the literature.27,28 There is no obvious explanation for this finding. All reasonable measures were taken to avoid interference by drugs or food, and none of the patients had evidence of malabsorption syndromes or other gastrointestinal conditions.

In view of previously reported experience with mucuna, our observations of much higher peak L-dopa concentrations and larger AUCs on mucuna are unexpected and surprising. A possible explanation may lie in the administration of mucuna as a suspension: L-dopa is mainly absorbed from the proximal small intestine, and delays in reaching the duodenum through the gastric valve are likely to occur more commonly with any form of coating than with dispersible formulations. This explains why dispersible L-dopa works more quickly than standard preparations. The latency to the onset of a clinical effect with dispersible L-dopa has been reported to be on average 26.820 or 27.9 min19 and is thus comparable to the mean latency of 34.6 min observed in our patients with 30 g mucuna.

Additives contained in the mucuna powder preparation may also have had an impact on absorption: the seed powder preparation used in this study was produced with the aim of achieving as standardised a composition as possible. The small amount of ascorbic acid, added for chemical stability,30 may potentially have enhanced intestinal absorption.31 Citric acid is also known to have some effect on L-dopa absorption,32 but the addition of a small amount of citric acid does not seem likely to be a sufficient explanation for such a marked difference in pharmacokinetics. Some other additives differed slightly from those found in the commonly used commercial Indian preparations, and further investigations into factors that may promote gastrointestinal absorption of the seed powder compound are warranted.

Decarboxylase inhibitors were shown to prolong L-dopa t1/2; to a moderate degree in most12,24,27 but not all9,33 studies. In contrast, our own data show a similar rate of decline of L-dopa plasma concentrations with 30 g mucuna and LD/CD. Although a small residual effect from patients’ on going carbidopa medication cannot be excluded due to its plasma t1/2; of 3 h, the similarity in the plasma concentration decline between LD/CD and 30 g mucuna raises the possibility of an additional active ingredient in the mucuna preparation with a blocking effect on L-dopa degradation. However, there is as yet no direct evidence of such active agents contained in the plant preparation.

The metabolite 3-OMD showed very similar AUC on mucuna and LD/CD, despite higher peak plasma concentrations of L-dopa with 30 g mucuna. This can largely be explained by the fact that in the absence of a decarboxylase inhibitor in the mucuna preparation, L-dopa was predominantly metabolised by decarboxylation, leading to smaller concentrations of 3-OMD.

The combination of rapid onset of action with long duration of effect appears to constitute a characteristic of this plant preparation. Previous limited pharmacokinetic reports with mucuna preparations suggested a lower bioavailability of mucuna with a somewhat slower increase and decline of L-dopa plasma concentrations and a lower peak.34 However, these comparisons were done with historical controls rather than in a controlled comparison. In contrast, our findings indicate that mucuna formulation may actually have a higher bioavailability than standard LD/CD which may not be explained by dose alone.

It is also noteworthy that despite larger mean L-dopa concentrations associated with 30 g mucuna, there were no significant differences in dyskinesia severity during the challenges. Although both the longer duration of effect and the larger AUC can in part be explained by higher maximum concentrations reached with 30 g mucuna,35 the differences are striking and raise the possibility of additional explanations.

Another aim of this study was to compare the clinical efficacy and tolerability of the two doses of the mucuna preparation. While a dose of 30 g of the mucuna preparation led to reliable and sustained antiparkinsonian effects in all patients, this did not always occur with the 15 g dose, and pharmacokinetic results clearly showed that L-dopa concentrations were considerably lower with the smaller dose.

Tolerability was comparable with all three study drugs. Adverse effects were mild and shortlasting, and the patient who dropped out from the study due to vomiting on 30 g mucuna fully recovered within a few minutes, and was prepared to stay in the trial. The assessment was discontinued, however, because part of the ingested drug was likely to have become unavailable for absorption.

Acute side effects of L-dopa such as nausea, vomiting, and orthostatic hypotension have been shown to be correlated with plasma concentrations9 and to occur less often in the presence of a decarboxylase inhibitor.9,36 In view of the significantly higher plasma concentrations reached with 30 g mucuna than LD/CD, it is encouraging that side effect profiles were similar in our study. However, this lack of difference may have been partly due to the fact that tachyphylaxis and peripheral tolerance to dopamine receptor stimulation occur with chronic L-dopa administration, and different results may have been seen in de novo patients. It might be appropriate to administer mucuna preparation in combination with a peripheral dopa decarboxylase inhibitor which may further improve tolerability and efficacy.

The combination of M pruriens with domperidone, which blocks peripheral dopamine receptors, would also be expected to reduce peripheral adverse events. Domperidone was not used in this study because it has been shown to slightly improve L-dopa absorption.37

M pruriens grows widely throughout the tropics and is currently mostly planted to improve soil and provide animal feed, and to a smaller extent, for human consumption. It is believed the biological purpose of the L-dopa concentration is to protect the plant against insect attack. Mucuna contains larger amounts of L-dopa than any other known natural source.38,39 Further natural sources of L-dopa include other members of the mucuna genus, such as Stizolobium deeringianum,40 and Vicia fava (broad bean), in which L-dopa was identified in 1913.41 An open-label study of 250 g of cooked V fava compared with 100 mg synthetic LD/CD showed lower peak plasma concentrations following the bean meal, and pharmacokinetic profile and clinical effects very similar to synthetic L-dopa.42 In an uncontrolled study,38 one patient failed to switch on altogether following 150 g of V fava. Clinical benefit from longer term use has also been reported in an uncontrolled fashion.43 Although limited conclusions are possible in the absence of randomised, double blind investigations of V fava, there is no suggestion in the reported literature that it might share the pharmacokinetic properties of mucuna found in our study. Moreover, the use of V fava for the treatment of PD also has practical limitations: the much lower L-dopa content in V fava compared with mucuna requires the ingestion of bulky meals, and there is a risk of favism, a haemolytic anaemia which can occur in persons with a genetic deficiency of the enzyme glucose 6-phosphate dehydrogenase.

Recent animal data44 have suggested anti-lipid peroxidation effects of an alcohol extract of M pruriens. If confirmed in further studies, this raises the possibility of an additional beneficial role for mucuna.

Based on this preliminary pilot study in patients with PD and short duration L-dopa response, the 30 g M pruriens formulation seems to possess potential advantages over existing commercially available controlled release or dispersible formulations of L-dopa in that it combines a rapid onset of action with a slightly longer duration of therapeutic response compared with a dose of standard L-dopa calculated on the basis of the known quantity of L-dopa in mucuna using standard conversion ratios. No increase in dyskinesia severity or in peripheral dopaminergic adverse events was found on the mucuna preparation. Further analysis of the seeds’ content may reveal further explanations for the differences in the pharmacokinetic profiles found in this study. If these findings can be confirmed in larger and longer term studies, mucuna would seem to be a reasonable commercially viable alternative to standard L-dopa.

much more so than the raw powder for me at least. just wondered if it was a phase i was going through.

If it's a diuretic, is it affecting your blood pressure?