Physicochemistry in medicine: some selected examples

International audienc

Characterization and Some Physicochemical Aspects of Pathological Microcalcifications

Several major diseases, such as cancer and cardiovascular abnormalities, may be linked to pathological deposition of minerals or organic compounds in various tissues. Thus, the detection of such minerals or compounds and understanding the physicochemical processes associated with their formation are essential. As underlined by Schmidt et al., in Europe and the U.S., breast cancer will occur in 1 in 10 women. If clustered calcifications are one of the mammographic signs of early breast cancer, their chemical nature must be determined. More precisely, calcium phosphates (CaPs) are frequently associated with malignancy, but calcium oxalates are present in benign lesions. From a medical viewpoint, pathological calcifications refer to at least three very different families of biominerals: concretions, metastatic calcifications and dystrophic calcifications. Concretions are found in hollow organs or ducts of the body. For example, kidney stones are solid concretions of dissolved minerals in urine found in the kidney. In contrast, metastatic and dystrophic calcifications, which can be considered ectopic calcifications, are defined as unexpected biomineralization occurring in soft tissues. In the absence of a systemic mineral imbalance, dystrophic calcification is often associated with tissue alteration or necrosis. In contrast, metastatic calcifications resulting from mineral imbalance are more systemic and affect various tissues (e.g., vessels, lungs, kidneys). A fourth family can be considered physiological calcification (bone), which becomes pathological with diseases such as arthrosis or osteoporosis

High Zn content of Randall's plaque: A μ-X-ray fluorescence investigation

Kidney stone disease, or nephrolithiasis, is a common ailment. Among the different risk factors usually associated with nephrolithiasis are dehydration, metabolic defects (especially with regard to calcium and oxalate). The presence of a mineral deposit at the surface of the renal papilla (termed Randall's plaque) has all been recently underlined. Of note, Randall's plaque is made of the calcium phosphate, carbapatite, and serves as a nucleus for kidney stone formation. The process by which apatite nanocrystals nucleate and form Randall's plaque remains unclear. This paper deals with the possible relationship between trace elements and the formation of this mineral. The investigation has been performed on a set of Randall's plaques, extracted from human kidney stones, through μ-X-ray diffraction and μ-X-ray fluorescence analyses in order to determine the chemical composition of the plaque as well as the nature and the amount of trace elements. Our data provide evidence that Zn levels are dramatically increased in carbapatite of RP by comparison to carbapatite in kidney stones, suggesting that calcified deposits within the medullar interstitium are a pathological process involving a tissue reaction. Further studies, perhaps including the investigation of biomarkers for inflammation, are necessary for clarifying the role of Zn in Randall's plaque formation

Therapy modifies cystine kidney stones at the macroscopic scale. Do such alterations exist at the mesoscopic and nanometre scale?

International audienceWith an incidence of 1:7000 births, cystinuria, the most frequent cause of stone formation among genetic diseases, represents a major medical problem. Twentyfive cystine stones randomly selected from cystinuric patients were investigated. From a crystallographic point of view, cystine stones are composed of micrometre size crystallites, which are made up of an aggregation of nanocrystals. Through scanning electron microscopy, the morphology and size of the crystallites have been described, while the size of the nanocrystals was investigated by means of powder neutron diffraction. Powder neutron diffraction analysis and/or scanning electron microscopy examination of cystine stones provide evidence that usual alkalinization by sodium bicarbonate associated with high diuresis significantly reduces the size of both nanocrystals and crystallites, while for other treatments, including alkalinizing drugs and thiol derivatives, the data suggest mainly changes in the topology of crystallites. Alkalinization with sodium bicarbonate affects cystine kidney stones at the mesoscopic and nanoscopic scales, while other medical treatments only alter their surface. Such an approach may help to assess the interaction between drugs and cystine stones in cystinuric patients

SEM-EDX micro-analysis and FTIR infrared microscopy by ATR of a bladder stone from the IIIth millennium BC from the B1S passage-grave of the necropolis in Chenon (Charente, France)

Here is a case of bladder stone of average size dated to the Late Neolithic period, found in the multiple burial of the B1S passage-grave in Chenon (Charente, France). Chemical analysis showed a mixed composition. The core, intermediate and surface envelopes consist in calcium phosphate apatite associated with whitlockite and amorphous carbonated calcium phosphate, all clarified by Fourier Transform InfraRed spectroscopy. Calcium phosphatic stones are characteristic of communities, such as those of the Neolithic period, where the diet was rich in cereal carbohydrates and poor in animal proteins. The excavation of such extra-skeletal objects is an event that is particularly interesting as it provides documents on the history of diseases and diets in ancient populations. The complete set of data suggests that this bladder stone was formed during a urinary tract infection with a germ possessing a very active urease

The type Ic morphology of urinary calculi: an alert to primary hyperoxaluria? Experience with 43 Moroccan children

Primary hyperoxaluria is the most severe stone disease responsible for multiple stone recurrence and impairment of kidney function. It is a rare inherited disease with an autosomal transmission. Due to the high proportion of consanguineous marriages by comparison to other areas in the world, this pathology is more frequent in North Africa. Stones are made of calcium oxalate monohydrate, which is not unique to the disease and cannot help physicians for the diagnosis. By contrast, stone morphology may be a useful marker of the pathology. We report our experience based on 614 stones from Moroccan children analyzed by infrared spectroscopy and examined by stereomicroscopy for the determination of their morphological type. Our results show that 85 stones (13.8%) exhibit a type Ic morphology, strongly suggestive of the disease in children patients. It was confirmed in all subjects of a subgroup of 43 patients who benefited from urinary biochemical explorations revealing whewellite crystalluria and a very high oxalate to creatinine ratio

SEM-EDX micro-analysis and FTIR infrared microscopy by ATR of a bladder stone from the IIIth millennium BC from the B1S passage-grave of the necropolis in Chenon (Charente, France)

Here is a case of bladder stone of average size dated to the Late Neolithic period, found in the multiple burial of the B1S passage-grave in Chenon (Charente, France). Chemical analysis showed a mixed composition. The core, intermediate and surface envelopes consist in calcium phosphate apatite associated with whitlockite and amorphous carbonated calcium phosphate, all clarified by Fourier Transform InfraRed spectroscopy. Calcium phosphatic stones are characteristic of communities, such as those of the Neolithic period, where the diet was rich in cereal carbohydrates and poor in animal proteins. The excavation of such extra-skeletal objects is an event that is particularly interesting as it provides documents on the history of diseases and diets in ancient populations. The complete set of data suggests that this bladder stone was formed during a urinary tract infection with a germ possessing a very active urease